Ignet

Gene Information

Gene symbol: TRPC6

Gene name: transient receptor potential cation channel, subfamily C, member 6

HGNC ID: 12338

Synonyms: TRP6

Related Genes

#	Gene Symbol	Number of hits
1	ACE	1 hits
2	ACTN4	1 hits
3	AGT	1 hits
4	AGTR1	1 hits
5	AKT1	1 hits
6	ALB	1 hits
7	BAX	1 hits
8	BCL2	1 hits
9	CAMK2G	1 hits
10	CAMK4	1 hits
11	CASP3	1 hits
12	CD2	1 hits
13	CD2AP	1 hits
14	CDK5	1 hits
15	CLU	1 hits
16	COL4A2	1 hits
17	COL4A5	1 hits
18	CRTC1	1 hits
19	CRTC2	1 hits
20	CSE	1 hits
21	CYBB	1 hits
22	DUOX1	1 hits
23	DUOX2	1 hits
24	EGF	1 hits
25	EGFR	1 hits
26	EPO	1 hits
27	GLP1R	1 hits
28	GRIA1	1 hits
29	GSTCD	1 hits
30	INF2	1 hits
31	INS	1 hits
32	KCNA5	1 hits
33	KCNMA1	1 hits
34	KL	1 hits
35	LAMB2	1 hits
36	LMX1A	1 hits
37	LMX1B	1 hits
38	MAGI1	1 hits
39	MAPK1	1 hits
40	MAPK3	1 hits
41	MAPK6	1 hits
42	MGAT1	1 hits
43	MT-TL1	1 hits
44	MYH9	1 hits
45	NFATC1	1 hits
46	NFATC3	1 hits
47	NFKB1	1 hits
48	NOD2	1 hits
49	NOX4	1 hits
50	NOX5	1 hits
51	NPHS1	1 hits
52	NPHS2	1 hits
53	NPY6R	1 hits
54	P2RX4	1 hits
55	P2RY2	1 hits
56	PDE5A	1 hits
57	PDLIM5	1 hits
58	PIK3CA	1 hits
59	PKD2	1 hits
60	PLA2G1B	1 hits
61	PLCB1	1 hits
62	PLCE1	1 hits
63	PLCG1	1 hits
64	PLCL1	1 hits
65	PPARA	1 hits
66	PPP3CA	1 hits
67	PPP3CB	1 hits
68	PPP3R1	1 hits
69	PRKCA	1 hits
70	RELA	1 hits
71	REN	1 hits
72	RHOD	1 hits
73	SCARB2	1 hits
74	SDC4	1 hits
75	SETD2	1 hits
76	SMAD3	1 hits
77	SMARCA1	1 hits
78	SOD1	1 hits
79	SRPSMCR	1 hits
80	STAT3	1 hits
81	SYNPO	1 hits
82	TLN1	1 hits
83	TMEM208	1 hits
84	TNF	1 hits
85	TRPA1	1 hits
86	TRPC1	1 hits
87	TRPC2	1 hits
88	TRPC3	1 hits
89	TRPC4	1 hits
90	TRPC5	1 hits
91	TRPC7	1 hits
92	TRPM2	1 hits
93	TRPM6	1 hits
94	TRPV1	1 hits
95	TRPV4	1 hits
96	VEGFA	1 hits
97	WIPI1	1 hits
98	WT1	1 hits
99	ZEB2	1 hits

Related Sentences

#	PMID	Sentence
1	15975974	In addition, a striking number of biological functions have already been assigned to the various TRPC proteins, including mechanosensing activity (TRPC1), chemotropic axon guidance (TRPC1 and TRPC3), pheromone sensing and the regulation of sexual and social behaviour (TRPC2), endothelial-dependent regulation of vascular tone, endothelial permeability and neurotransmitter release (TRPC4), axonal growth (TRPC5), modulation of smooth muscle tone in blood vessels and lung and regulation of podocyte structure and function in the kidney (TRPC6).
2	16303855	TRPC1 colocalized with aquaporin-1, a marker for proximal tubule and thin descending limb, but not with aquaporin-2, a marker for connecting tubule and collecting duct cells.
3	16303855	TRPC3 and -C6 colocalized with aquaporin-2, but not with the Na(+)/Ca(2+) exchanger or peanut lectin.
4	16303855	In polarized cultures of M1 and IMCD-3 collecting duct cells, TRPC3 was localized exclusively to the apical domain, whereas TRPC6 was found in both the basolateral and apical membranes.
5	16303855	TRPC3 and TRPC6 were also detected in primary podocyte cultures, whereas TRPC1 was exclusively expressed in mesangial cell cultures.
6	16303855	These results suggest that TRPC1, -C3, and -C6 may play a functional role in PLC-dependent signaling in specific regions of the nephron.
7	16303855	TRPC1 colocalized with aquaporin-1, a marker for proximal tubule and thin descending limb, but not with aquaporin-2, a marker for connecting tubule and collecting duct cells.
8	16303855	TRPC3 and -C6 colocalized with aquaporin-2, but not with the Na(+)/Ca(2+) exchanger or peanut lectin.
9	16303855	In polarized cultures of M1 and IMCD-3 collecting duct cells, TRPC3 was localized exclusively to the apical domain, whereas TRPC6 was found in both the basolateral and apical membranes.
10	16303855	TRPC3 and TRPC6 were also detected in primary podocyte cultures, whereas TRPC1 was exclusively expressed in mesangial cell cultures.
11	16303855	These results suggest that TRPC1, -C3, and -C6 may play a functional role in PLC-dependent signaling in specific regions of the nephron.
12	16628251	Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6.
13	16628251	Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage.
14	16628251	These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1.
15	16752799	Seven genes have been recognized till present, which mutations are responsible for severe forms of NS: NPHS1, NPHS2, ACTN4, CD2AP and WT1, TRPC6, LAMB2.
16	16752799	Proteins encoded by these genes (nephrin, podocin, alpha-actinin-4, an adapter protein anchoring CD2 and others) influence the function of the podocytes.
17	16752799	It was concluded that patients with steroid resistant nephrotic syndrome (SRNS) with homozygous or compound heterozygous mutations in NPHS2 have reduced risk for recurrence of focal segmental glomerulosclerosis (FSGS) in renal transplant (only 8% in comparison with 35% in patients without mutation in NPHS2).
18	16752799	This polymorphism appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele.
19	16752799	There are also 3 genetic loci connected with autosomal dominant forms of FSGS: ACTN4, TRPC6 and CD2AP (found only in the mice models).
20	16752799	Seven genes have been recognized till present, which mutations are responsible for severe forms of NS: NPHS1, NPHS2, ACTN4, CD2AP and WT1, TRPC6, LAMB2.
21	16752799	Proteins encoded by these genes (nephrin, podocin, alpha-actinin-4, an adapter protein anchoring CD2 and others) influence the function of the podocytes.
22	16752799	It was concluded that patients with steroid resistant nephrotic syndrome (SRNS) with homozygous or compound heterozygous mutations in NPHS2 have reduced risk for recurrence of focal segmental glomerulosclerosis (FSGS) in renal transplant (only 8% in comparison with 35% in patients without mutation in NPHS2).
23	16752799	This polymorphism appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele.
24	16752799	There are also 3 genetic loci connected with autosomal dominant forms of FSGS: ACTN4, TRPC6 and CD2AP (found only in the mice models).
25	17459670	TRPC6 and FSGS: the latest TRP channelopathy.
26	17459670	Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.
27	17459670	The latest advance in familial FSGS has been the discovery of a mutant form of canonical transient receptor potential cation channel 6 (TRPC6), which causes an increase in calcium transients and essentially a gain of function in this cation channel located on the podocyte cell membrane.
28	17459670	TRPC6 channels have been shown to be activated via phospholipase C stimulation.
29	17459670	Mutant TRPC6 may also amplify injurious signals mediated by Ang II, a common final pathway of podocyte apoptosis in various mammalian species.
30	17459670	Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis.
31	17459670	This creates the exciting possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.
32	17459670	TRPC6 and FSGS: the latest TRP channelopathy.
33	17459670	Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.
34	17459670	The latest advance in familial FSGS has been the discovery of a mutant form of canonical transient receptor potential cation channel 6 (TRPC6), which causes an increase in calcium transients and essentially a gain of function in this cation channel located on the podocyte cell membrane.
35	17459670	TRPC6 channels have been shown to be activated via phospholipase C stimulation.
36	17459670	Mutant TRPC6 may also amplify injurious signals mediated by Ang II, a common final pathway of podocyte apoptosis in various mammalian species.
37	17459670	Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis.
38	17459670	This creates the exciting possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.
39	17459670	TRPC6 and FSGS: the latest TRP channelopathy.
40	17459670	Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.
41	17459670	The latest advance in familial FSGS has been the discovery of a mutant form of canonical transient receptor potential cation channel 6 (TRPC6), which causes an increase in calcium transients and essentially a gain of function in this cation channel located on the podocyte cell membrane.
42	17459670	TRPC6 channels have been shown to be activated via phospholipase C stimulation.
43	17459670	Mutant TRPC6 may also amplify injurious signals mediated by Ang II, a common final pathway of podocyte apoptosis in various mammalian species.
44	17459670	Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis.
45	17459670	This creates the exciting possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.
46	17459670	TRPC6 and FSGS: the latest TRP channelopathy.
47	17459670	Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.
48	17459670	The latest advance in familial FSGS has been the discovery of a mutant form of canonical transient receptor potential cation channel 6 (TRPC6), which causes an increase in calcium transients and essentially a gain of function in this cation channel located on the podocyte cell membrane.
49	17459670	TRPC6 channels have been shown to be activated via phospholipase C stimulation.
50	17459670	Mutant TRPC6 may also amplify injurious signals mediated by Ang II, a common final pathway of podocyte apoptosis in various mammalian species.
51	17459670	Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis.
52	17459670	This creates the exciting possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.
53	17459670	TRPC6 and FSGS: the latest TRP channelopathy.
54	17459670	Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.
55	17459670	The latest advance in familial FSGS has been the discovery of a mutant form of canonical transient receptor potential cation channel 6 (TRPC6), which causes an increase in calcium transients and essentially a gain of function in this cation channel located on the podocyte cell membrane.
56	17459670	TRPC6 channels have been shown to be activated via phospholipase C stimulation.
57	17459670	Mutant TRPC6 may also amplify injurious signals mediated by Ang II, a common final pathway of podocyte apoptosis in various mammalian species.
58	17459670	Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis.
59	17459670	This creates the exciting possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.
60	17459670	TRPC6 and FSGS: the latest TRP channelopathy.
61	17459670	Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.
62	17459670	The latest advance in familial FSGS has been the discovery of a mutant form of canonical transient receptor potential cation channel 6 (TRPC6), which causes an increase in calcium transients and essentially a gain of function in this cation channel located on the podocyte cell membrane.
63	17459670	TRPC6 channels have been shown to be activated via phospholipase C stimulation.
64	17459670	Mutant TRPC6 may also amplify injurious signals mediated by Ang II, a common final pathway of podocyte apoptosis in various mammalian species.
65	17459670	Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis.
66	17459670	This creates the exciting possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.
67	17530296	Renin-angiotensin axis blockade reduces proteinuria in presymptomatic patients with familial FSGS.
68	17530296	Familial and genetic forms of focal segmental glomerulosclerosis (FSGS) are associated with six different mutations in genes affecting the podocyte (NPHS2, ACTN4, CD2AP, WT1, TRPC6, and PLCE1).
69	17530296	We describe three children from two different families with familial FSGS in whom partial to complete remission of proteinuria was attained through early blockade of the renin-angiotensin axis.
70	17530296	We speculate that presymptomatic patients with normal renal function who have genetic or familial FSGS may benefit from early blockade of the renin-angiotensin axis and that this may also prevent progressive renal disease.
71	17570936	In the context of the slit diaphragm signaling network, TRPC6 is clustered and regulated by a podocin-lipid complex that might translate mechanical tension to ion channel action.
72	18378501	Expression of trpC1 and trpC6 orthologs in zebrafish.
73	18378501	TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes.
74	18378501	Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease.
75	18378501	To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development.
76	18378501	We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells.
77	18378501	Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types.
78	18378501	Expression of trpC1 and trpC6 orthologs in zebrafish.
79	18378501	TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes.
80	18378501	Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease.
81	18378501	To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development.
82	18378501	We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells.
83	18378501	Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types.
84	18378501	Expression of trpC1 and trpC6 orthologs in zebrafish.
85	18378501	TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes.
86	18378501	Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease.
87	18378501	To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development.
88	18378501	We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells.
89	18378501	Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types.
90	18378501	Expression of trpC1 and trpC6 orthologs in zebrafish.
91	18378501	TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes.
92	18378501	Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease.
93	18378501	To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development.
94	18378501	We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells.
95	18378501	Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types.
96	18378501	Expression of trpC1 and trpC6 orthologs in zebrafish.
97	18378501	TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes.
98	18378501	Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease.
99	18378501	To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development.
100	18378501	We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells.
101	18378501	Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types.
102	18378501	Expression of trpC1 and trpC6 orthologs in zebrafish.
103	18378501	TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes.
104	18378501	Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease.
105	18378501	To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development.
106	18378501	We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells.
107	18378501	Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types.
108	18434567	In this article, I discuss the phenotypic characteristics of hereditary FSGS and the transient receptor potential cation channel 6 (TRPC6) protein, which is the genetic impetus for an autosomal dominant form of FSGS.
109	19129465	Activation of NFAT by TRPC6 mutants is blocked by inhibitors of calcineurin, calmodulin-dependent kinase II, and phosphatidylinositol 3-kinase.
110	19129465	PP2 partially inhibits NFAT activation by mutant TRPC6 independently of Src, Yes, or Fyn.
111	19129465	Activation of NFAT by TRPC6 mutants is blocked by inhibitors of calcineurin, calmodulin-dependent kinase II, and phosphatidylinositol 3-kinase.
112	19129465	PP2 partially inhibits NFAT activation by mutant TRPC6 independently of Src, Yes, or Fyn.
113	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
114	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
115	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
116	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
117	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
118	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
119	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
120	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
121	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
122	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
123	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
124	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
125	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
126	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
127	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
128	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
129	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
130	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
131	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
132	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
133	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
134	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
135	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
136	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
137	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
138	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
139	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
140	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
141	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
142	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
143	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
144	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
145	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
146	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
147	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
148	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
149	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
150	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
151	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
152	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
153	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
154	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
155	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
156	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
157	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
158	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
159	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
160	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
161	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
162	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
163	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
164	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
165	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
166	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
167	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
168	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
169	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
170	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
171	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
172	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
173	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
174	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
175	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
176	19546355	TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation.
177	19546355	Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane.
178	19546355	The present study evaluated the alteration of TRPC6 expression and the Ca(2+) influx involved in Ang II-induced podocyte apoptosis.
179	19546355	The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated.
180	19546355	The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca(2+) concentration was elevated.
181	19546355	By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca(2+) influx were inhibited.
182	19546355	Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-kappaB (NF-kappaB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased.
183	19546355	Moreover, the translocation of NF-kappaB in nucleus resulted from Ang II was reduced by treatment with U0126.
184	19546355	The activation of ERK pathway and subsequent translocation of NF-kappaB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
185	19562370	Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin beta2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome.
186	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
187	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
188	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
189	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
190	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
191	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
192	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
193	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
194	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
195	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
196	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
197	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
198	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
199	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
200	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
201	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
202	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
203	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
204	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
205	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
206	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
207	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
208	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
209	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
210	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
211	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
212	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
213	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
214	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
215	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
216	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
217	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
218	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
219	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
220	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
221	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
222	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
223	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
224	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
225	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
226	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
227	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
228	19910702	NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury.
229	19910702	Recent studies have demonstrated upregulation of transient receptor potential cation channel 6 (TRPC6) contributes to podocyte injury in acquired forms of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS).
230	19910702	The present study tested the hypothesis that NADPH oxidase-mediated redox signaling importantly participates in the development of podocyte injury by regulation of TRPC6 expression and activity.
231	19910702	Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats.
232	19910702	Inhibition of NADPH oxidase activity by apocynin ameliorated proteinuria and podocyte effacement and reduced TRPC6 expression.
233	19910702	In in vitro study, PAN significantly increased NOX4 and TRPC6 expression levels in cultured podocytes.
234	19910702	Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling.
235	20209128	Injection of shamporter coupled with either nephrin siRNA or TRPC6 siRNA via tail vein into normal rats substantially reduced the protein levels of nephrin or TRPC6 respectively, measured by western blot analysis and immunostaining.
236	21220918	TGF-β1 induces podocyte injury through Smad3-ERK-NF-κB pathway and Fyn-dependent TRPC6 phosphorylation.
237	21220918	In addition, Western blot showed that TGF-β1 induced significant activation of p-Smad3, p-ERK and RelA/p65.
238	21220918	Importantly, obvious translocation of ERK and RelA/p65 to nuclei was observed in TGF-β1-treated podocyte, which was reduced by ERK inhibitor U0126.
239	21220918	Together, we provide evidences that TGF-β1 induces podocyte damage by upregulating TRPC6 protein most possibly through Smad3-ERK-NF-κB pathway, in which Fyn-dependent tyrosine phosphorylation of TRPC6 might exert a crucial role on the activation of its channel function.
240	21220918	TGF-β1 induces podocyte injury through Smad3-ERK-NF-κB pathway and Fyn-dependent TRPC6 phosphorylation.
241	21220918	In addition, Western blot showed that TGF-β1 induced significant activation of p-Smad3, p-ERK and RelA/p65.
242	21220918	Importantly, obvious translocation of ERK and RelA/p65 to nuclei was observed in TGF-β1-treated podocyte, which was reduced by ERK inhibitor U0126.
243	21220918	Together, we provide evidences that TGF-β1 induces podocyte damage by upregulating TRPC6 protein most possibly through Smad3-ERK-NF-κB pathway, in which Fyn-dependent tyrosine phosphorylation of TRPC6 might exert a crucial role on the activation of its channel function.
244	21258036	TRPC6 enhances angiotensin II-induced albuminuria.
245	21258036	Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS).
246	21258036	We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals.
247	21258036	To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days.
248	21258036	In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude.
249	21258036	Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
250	21258036	TRPC6 enhances angiotensin II-induced albuminuria.
251	21258036	Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS).
252	21258036	We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals.
253	21258036	To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days.
254	21258036	In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude.
255	21258036	Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
256	21258036	TRPC6 enhances angiotensin II-induced albuminuria.
257	21258036	Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS).
258	21258036	We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals.
259	21258036	To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days.
260	21258036	In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude.
261	21258036	Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
262	21258036	TRPC6 enhances angiotensin II-induced albuminuria.
263	21258036	Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS).
264	21258036	We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals.
265	21258036	To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days.
266	21258036	In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude.
267	21258036	Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
268	21258036	TRPC6 enhances angiotensin II-induced albuminuria.
269	21258036	Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS).
270	21258036	We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals.
271	21258036	To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days.
272	21258036	In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude.
273	21258036	Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
274	21258036	TRPC6 enhances angiotensin II-induced albuminuria.
275	21258036	Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS).
276	21258036	We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals.
277	21258036	To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days.
278	21258036	In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude.
279	21258036	Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
280	21321315	Transient receptor potential cation channel 6 (TRPC6) is one of the key molecules for filtration barrier function of podocytes.
281	21321315	To investigate the impact of TRPC6 over-expression in podocytes on its function and its relation to proteinuria in kidney diseases, we over-expressed TRPC6 in mouse podocytes by transient transfection of TRPC6 cDNA plasmid, and observed their changes in foot processes, intracellular F-actin distribution, nephrin and synaptopodin expression, electrophysiology, RhoA activity and intracellular Ca(2+).
282	21321315	These cells also displayed a higher increase of intracellular Ca(2+) ion to the TRPC6 agonist 1-oleoyl-acetyl-sn-glycerol and a higher current in the patch-clamp experiment, down-regulation of nephrin and synaptopodin expression and increase of activated RhoA.
283	21321315	Additionally, the podocytes over-expressing TRPC6 treated with RhoA inhibitor Y-27632 showed an improvement in F-actin arrangement in the cells and increase of nephrin and synaptopodin expression.
284	21321315	The increase of intracellular Ca(2+) down-regulates the expression of two important molecules, nephrin on slit diaphragm and synaptopodin in cytoskeleton, and stimulates RhoA activity, which in turn causes F-actin derangement and the decrease of foot processes.
285	21321315	Transient receptor potential cation channel 6 (TRPC6) is one of the key molecules for filtration barrier function of podocytes.
286	21321315	To investigate the impact of TRPC6 over-expression in podocytes on its function and its relation to proteinuria in kidney diseases, we over-expressed TRPC6 in mouse podocytes by transient transfection of TRPC6 cDNA plasmid, and observed their changes in foot processes, intracellular F-actin distribution, nephrin and synaptopodin expression, electrophysiology, RhoA activity and intracellular Ca(2+).
287	21321315	These cells also displayed a higher increase of intracellular Ca(2+) ion to the TRPC6 agonist 1-oleoyl-acetyl-sn-glycerol and a higher current in the patch-clamp experiment, down-regulation of nephrin and synaptopodin expression and increase of activated RhoA.
288	21321315	Additionally, the podocytes over-expressing TRPC6 treated with RhoA inhibitor Y-27632 showed an improvement in F-actin arrangement in the cells and increase of nephrin and synaptopodin expression.
289	21321315	The increase of intracellular Ca(2+) down-regulates the expression of two important molecules, nephrin on slit diaphragm and synaptopodin in cytoskeleton, and stimulates RhoA activity, which in turn causes F-actin derangement and the decrease of foot processes.
290	21321315	Transient receptor potential cation channel 6 (TRPC6) is one of the key molecules for filtration barrier function of podocytes.
291	21321315	To investigate the impact of TRPC6 over-expression in podocytes on its function and its relation to proteinuria in kidney diseases, we over-expressed TRPC6 in mouse podocytes by transient transfection of TRPC6 cDNA plasmid, and observed their changes in foot processes, intracellular F-actin distribution, nephrin and synaptopodin expression, electrophysiology, RhoA activity and intracellular Ca(2+).
292	21321315	These cells also displayed a higher increase of intracellular Ca(2+) ion to the TRPC6 agonist 1-oleoyl-acetyl-sn-glycerol and a higher current in the patch-clamp experiment, down-regulation of nephrin and synaptopodin expression and increase of activated RhoA.
293	21321315	Additionally, the podocytes over-expressing TRPC6 treated with RhoA inhibitor Y-27632 showed an improvement in F-actin arrangement in the cells and increase of nephrin and synaptopodin expression.
294	21321315	The increase of intracellular Ca(2+) down-regulates the expression of two important molecules, nephrin on slit diaphragm and synaptopodin in cytoskeleton, and stimulates RhoA activity, which in turn causes F-actin derangement and the decrease of foot processes.
295	21321315	Transient receptor potential cation channel 6 (TRPC6) is one of the key molecules for filtration barrier function of podocytes.
296	21321315	To investigate the impact of TRPC6 over-expression in podocytes on its function and its relation to proteinuria in kidney diseases, we over-expressed TRPC6 in mouse podocytes by transient transfection of TRPC6 cDNA plasmid, and observed their changes in foot processes, intracellular F-actin distribution, nephrin and synaptopodin expression, electrophysiology, RhoA activity and intracellular Ca(2+).
297	21321315	These cells also displayed a higher increase of intracellular Ca(2+) ion to the TRPC6 agonist 1-oleoyl-acetyl-sn-glycerol and a higher current in the patch-clamp experiment, down-regulation of nephrin and synaptopodin expression and increase of activated RhoA.
298	21321315	Additionally, the podocytes over-expressing TRPC6 treated with RhoA inhibitor Y-27632 showed an improvement in F-actin arrangement in the cells and increase of nephrin and synaptopodin expression.
299	21321315	The increase of intracellular Ca(2+) down-regulates the expression of two important molecules, nephrin on slit diaphragm and synaptopodin in cytoskeleton, and stimulates RhoA activity, which in turn causes F-actin derangement and the decrease of foot processes.
300	21660954	Large-conductance Ca(2+)-activated K(+) channels (BK(Ca) channels) encoded by the Slo1 gene are expressed in podocytes in a complex with multiple glomerular slit diaphragm proteins including nephrin, TRPC6 channels, and several different actin-binding proteins.
301	21660954	Insulin stimulation of BK(Ca) channels was detectable in 15 min and required activation of both Erk and Akt signaling cascades.
302	21660954	High glucose treatment also abolished the stimulatory effects of insulin on BK(Ca) current density, although insulin continued to increase phosphorylation of Erk and Akt under those conditions.
303	21839714	Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
304	21839714	Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells.
305	21839714	We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo.
306	21839714	In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner.
307	21839714	We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT).
308	21839714	Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
309	21839714	Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
310	21839714	Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells.
311	21839714	We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo.
312	21839714	In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner.
313	21839714	We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT).
314	21839714	Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
315	21839714	Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
316	21839714	Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells.
317	21839714	We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo.
318	21839714	In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner.
319	21839714	We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT).
320	21839714	Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
321	21839714	Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
322	21839714	Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells.
323	21839714	We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo.
324	21839714	In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner.
325	21839714	We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT).
326	21839714	Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
327	21839714	Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
328	21839714	Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells.
329	21839714	We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo.
330	21839714	In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner.
331	21839714	We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT).
332	21839714	Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
333	21839714	Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
334	21839714	Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells.
335	21839714	We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo.
336	21839714	In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner.
337	21839714	We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT).
338	21839714	Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
339	21980113	Balancing calcium signals through TRPC5 and TRPC6 in podocytes.
340	21980113	Six years ago, transient receptor potential canonical 6 (TRPC6) mutations were found in families with hereditary FSGS, and TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for this previously described, nonselective, cationic current in podocytes.
341	21980113	Balancing calcium signals through TRPC5 and TRPC6 in podocytes.
342	21980113	Six years ago, transient receptor potential canonical 6 (TRPC6) mutations were found in families with hereditary FSGS, and TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for this previously described, nonselective, cationic current in podocytes.
343	22031853	Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species.
344	22031853	Here, we show that insulin evokes a rapid increase in the surface expression of canonical transient receptor potential-6 channel (TRPC6) channels in cultured podocytes, but caused a decrease in surface expression of TRPC5.
345	22031853	The effects of insulin on TRPC6 were mimicked by treating podocytes with H(2)O(2).
346	22031853	Insulin treatment rapidly increased the generation of H(2)O(2) in podocytes, and it increased the surface expression of the NADPH oxidase NOX4 in cultured podocytes.
347	22031853	Basal and insulin-stimulated surface expression of TRPC6 were reduced by pretreatment with diphenylene iodonium, an inhibitor of NADPH oxidases and other flavin-dependent enzymes, by siRNA knockdown of NOX4, and by manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, a membrane-permeable mimetic of superoxide dismutase and catalase.
348	22031853	These observations suggest that insulin increases generation of ROS in part through activation of NADPH oxidases, and that this step contributes to modulation of podocyte TRPC6 channels.
349	22031853	Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species.
350	22031853	Here, we show that insulin evokes a rapid increase in the surface expression of canonical transient receptor potential-6 channel (TRPC6) channels in cultured podocytes, but caused a decrease in surface expression of TRPC5.
351	22031853	The effects of insulin on TRPC6 were mimicked by treating podocytes with H(2)O(2).
352	22031853	Insulin treatment rapidly increased the generation of H(2)O(2) in podocytes, and it increased the surface expression of the NADPH oxidase NOX4 in cultured podocytes.
353	22031853	Basal and insulin-stimulated surface expression of TRPC6 were reduced by pretreatment with diphenylene iodonium, an inhibitor of NADPH oxidases and other flavin-dependent enzymes, by siRNA knockdown of NOX4, and by manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, a membrane-permeable mimetic of superoxide dismutase and catalase.
354	22031853	These observations suggest that insulin increases generation of ROS in part through activation of NADPH oxidases, and that this step contributes to modulation of podocyte TRPC6 channels.
355	22031853	Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species.
356	22031853	Here, we show that insulin evokes a rapid increase in the surface expression of canonical transient receptor potential-6 channel (TRPC6) channels in cultured podocytes, but caused a decrease in surface expression of TRPC5.
357	22031853	The effects of insulin on TRPC6 were mimicked by treating podocytes with H(2)O(2).
358	22031853	Insulin treatment rapidly increased the generation of H(2)O(2) in podocytes, and it increased the surface expression of the NADPH oxidase NOX4 in cultured podocytes.
359	22031853	Basal and insulin-stimulated surface expression of TRPC6 were reduced by pretreatment with diphenylene iodonium, an inhibitor of NADPH oxidases and other flavin-dependent enzymes, by siRNA knockdown of NOX4, and by manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, a membrane-permeable mimetic of superoxide dismutase and catalase.
360	22031853	These observations suggest that insulin increases generation of ROS in part through activation of NADPH oxidases, and that this step contributes to modulation of podocyte TRPC6 channels.
361	22031853	Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species.
362	22031853	Here, we show that insulin evokes a rapid increase in the surface expression of canonical transient receptor potential-6 channel (TRPC6) channels in cultured podocytes, but caused a decrease in surface expression of TRPC5.
363	22031853	The effects of insulin on TRPC6 were mimicked by treating podocytes with H(2)O(2).
364	22031853	Insulin treatment rapidly increased the generation of H(2)O(2) in podocytes, and it increased the surface expression of the NADPH oxidase NOX4 in cultured podocytes.
365	22031853	Basal and insulin-stimulated surface expression of TRPC6 were reduced by pretreatment with diphenylene iodonium, an inhibitor of NADPH oxidases and other flavin-dependent enzymes, by siRNA knockdown of NOX4, and by manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, a membrane-permeable mimetic of superoxide dismutase and catalase.
366	22031853	These observations suggest that insulin increases generation of ROS in part through activation of NADPH oxidases, and that this step contributes to modulation of podocyte TRPC6 channels.
367	22031853	Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species.
368	22031853	Here, we show that insulin evokes a rapid increase in the surface expression of canonical transient receptor potential-6 channel (TRPC6) channels in cultured podocytes, but caused a decrease in surface expression of TRPC5.
369	22031853	The effects of insulin on TRPC6 were mimicked by treating podocytes with H(2)O(2).
370	22031853	Insulin treatment rapidly increased the generation of H(2)O(2) in podocytes, and it increased the surface expression of the NADPH oxidase NOX4 in cultured podocytes.
371	22031853	Basal and insulin-stimulated surface expression of TRPC6 were reduced by pretreatment with diphenylene iodonium, an inhibitor of NADPH oxidases and other flavin-dependent enzymes, by siRNA knockdown of NOX4, and by manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, a membrane-permeable mimetic of superoxide dismutase and catalase.
372	22031853	These observations suggest that insulin increases generation of ROS in part through activation of NADPH oxidases, and that this step contributes to modulation of podocyte TRPC6 channels.
373	22242226	TRPC6 in podocytes: questions and commentary on the article by Jiang et al., 'Over-expressing transient receptor potential cation channel 6 in podocytes induces cytoskeleton rearrangement through increases of intracellular Ca21 and RhoA activation'.
374	22249312	QLα12(LacZ+/Cre+) mice showed no changes in podocyte number, apoptosis, proliferation or Rho/Src activation.
375	22249312	Real-time PCR revealed no significant changes in Nphs1, Nphs2, Cd2ap or Trpc6 expression, but Col4a2 message was increased in younger and older mice, while Col4a5 was decreased in older mice.
376	22249312	Confocal microscopy revealed disordered collagen IVα1/2 staining in older mice and loss of α5 without changes in other collagen IV subunits.
377	22249312	Taken together, these studies suggest that Gα12 activation promotes glomerular injury without podocyte depletion through a novel mechanism regulating collagen (α)IV expression, and supports the notion that glomerular damage may accrue through persistent GPCR activation in podocytes.
378	22684555	The distribution of α-actinin-4 and α-tubulin was disrupted after treatment with PAN, which was reversed by knocking down TRPC6 gene.
379	22693670	The close relationships of slit diaphragm (SD) molecules such as nephrin, podocin, CD2-associated protein (CD2AP), a-actinin-4, transient receptor potential cation channel 6 (TRPC6), Densin and membrane-associated guanylate kinase inverted 1 (MAGI-1), α3β1 integrin, WT1, phospholipase C epsilon-1 (PLCE1), Lmx1b, and MYH9, and mitochondrial disorders and circulating factors in the pathogenesis of glomerular proteinuria were also gradually discovered.
380	22782578	Key genes that have been identified from the study of inherited nephrotic syndromes include those encoding nephrin, podocin, TRPC6 (transient receptor potential canonical channel-6) and α-actinin-4, and more remain to be found.
381	23535151	Recombinant human erythropoietin pretreatment alleviates renal glomerular injury induced by cardiopulmonary bypass by reducing transient receptor potential channel 6-nuclear factor of activated T-cells pathway activation.
382	23570668	In this study, we report that high levels of glucose enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) influx, but glucose levels did not affect TRPC1 and TRPC5 expression.
383	23645677	Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular signal-regulated kinases 1/2 (ERK1/2).
384	23645677	The ERK1/2 MAPKs are activated in glomeruli and podocytes in several proteinuric disease models.
385	23645677	In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased ERK1/2 phosphorylation, an effect dependent upon channel function.
386	23645677	Through medium transfer experiments, we uncovered two distinct mechanisms for ERK activation by mutant TRPC6, a cell-autonomous, EGF receptor-independent mechanism and a non-cell-autonomous mechanism involving metalloprotease-mediated release of a presumed EGF receptor ligand.
387	23645677	Phosphorylation of Thr-70, Ser-282, and Tyr-31/285 were not necessary for ERK activation by mutant TRPC6, although a phosphomimetic TRPC6 S282E mutant was capable of ERK activation.
388	23645677	Taken together, these results identify two pathways downstream of mutant TRPC6 leading to ERK activation that may play a role in the development of FSGS.
389	23645677	Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular signal-regulated kinases 1/2 (ERK1/2).
390	23645677	The ERK1/2 MAPKs are activated in glomeruli and podocytes in several proteinuric disease models.
391	23645677	In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased ERK1/2 phosphorylation, an effect dependent upon channel function.
392	23645677	Through medium transfer experiments, we uncovered two distinct mechanisms for ERK activation by mutant TRPC6, a cell-autonomous, EGF receptor-independent mechanism and a non-cell-autonomous mechanism involving metalloprotease-mediated release of a presumed EGF receptor ligand.
393	23645677	Phosphorylation of Thr-70, Ser-282, and Tyr-31/285 were not necessary for ERK activation by mutant TRPC6, although a phosphomimetic TRPC6 S282E mutant was capable of ERK activation.
394	23645677	Taken together, these results identify two pathways downstream of mutant TRPC6 leading to ERK activation that may play a role in the development of FSGS.
395	23645677	Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular signal-regulated kinases 1/2 (ERK1/2).
396	23645677	The ERK1/2 MAPKs are activated in glomeruli and podocytes in several proteinuric disease models.
397	23645677	In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased ERK1/2 phosphorylation, an effect dependent upon channel function.
398	23645677	Through medium transfer experiments, we uncovered two distinct mechanisms for ERK activation by mutant TRPC6, a cell-autonomous, EGF receptor-independent mechanism and a non-cell-autonomous mechanism involving metalloprotease-mediated release of a presumed EGF receptor ligand.
399	23645677	Phosphorylation of Thr-70, Ser-282, and Tyr-31/285 were not necessary for ERK activation by mutant TRPC6, although a phosphomimetic TRPC6 S282E mutant was capable of ERK activation.
400	23645677	Taken together, these results identify two pathways downstream of mutant TRPC6 leading to ERK activation that may play a role in the development of FSGS.
401	23645677	Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular signal-regulated kinases 1/2 (ERK1/2).
402	23645677	The ERK1/2 MAPKs are activated in glomeruli and podocytes in several proteinuric disease models.
403	23645677	In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased ERK1/2 phosphorylation, an effect dependent upon channel function.
404	23645677	Through medium transfer experiments, we uncovered two distinct mechanisms for ERK activation by mutant TRPC6, a cell-autonomous, EGF receptor-independent mechanism and a non-cell-autonomous mechanism involving metalloprotease-mediated release of a presumed EGF receptor ligand.
405	23645677	Phosphorylation of Thr-70, Ser-282, and Tyr-31/285 were not necessary for ERK activation by mutant TRPC6, although a phosphomimetic TRPC6 S282E mutant was capable of ERK activation.
406	23645677	Taken together, these results identify two pathways downstream of mutant TRPC6 leading to ERK activation that may play a role in the development of FSGS.
407	23645677	Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular signal-regulated kinases 1/2 (ERK1/2).
408	23645677	The ERK1/2 MAPKs are activated in glomeruli and podocytes in several proteinuric disease models.
409	23645677	In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased ERK1/2 phosphorylation, an effect dependent upon channel function.
410	23645677	Through medium transfer experiments, we uncovered two distinct mechanisms for ERK activation by mutant TRPC6, a cell-autonomous, EGF receptor-independent mechanism and a non-cell-autonomous mechanism involving metalloprotease-mediated release of a presumed EGF receptor ligand.
411	23645677	Phosphorylation of Thr-70, Ser-282, and Tyr-31/285 were not necessary for ERK activation by mutant TRPC6, although a phosphomimetic TRPC6 S282E mutant was capable of ERK activation.
412	23645677	Taken together, these results identify two pathways downstream of mutant TRPC6 leading to ERK activation that may play a role in the development of FSGS.
413	23763262	The primary purpose of this review is to address the progress towards small molecule modulators of human Transient Receptor Potential Canonical proteins (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7).
414	23856489	Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated podocyte TRPC6 channels in hyperhomocysteinemia.
415	23856489	The present study was designed to investigate the contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular innate immunity mediator, to the development of glomerulosclerosis in hHcys.
416	23856489	We further discovered the novel role of NOD2 in mediating Ca(2+) signaling and found that homocysteine-induced NOD2 expression enhanced transient receptor potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca(2+) release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis.
417	23856489	Moreover, we found that nephrin expression was downregulated dependently by NOD2, and overexpression of nephrin attenuated homocysteine-induced TRPC6 expression in podocytes.
418	23856489	The results add evidence to support the essential role of nephrin in mediating NOD2-induced TRPC6 expression in hHcys.
419	23856489	In conclusion, our results for the first time establish a previously unknown function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury.
420	23856489	Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated podocyte TRPC6 channels in hyperhomocysteinemia.
421	23856489	The present study was designed to investigate the contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular innate immunity mediator, to the development of glomerulosclerosis in hHcys.
422	23856489	We further discovered the novel role of NOD2 in mediating Ca(2+) signaling and found that homocysteine-induced NOD2 expression enhanced transient receptor potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca(2+) release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis.
423	23856489	Moreover, we found that nephrin expression was downregulated dependently by NOD2, and overexpression of nephrin attenuated homocysteine-induced TRPC6 expression in podocytes.
424	23856489	The results add evidence to support the essential role of nephrin in mediating NOD2-induced TRPC6 expression in hHcys.
425	23856489	In conclusion, our results for the first time establish a previously unknown function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury.
426	23856489	Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated podocyte TRPC6 channels in hyperhomocysteinemia.
427	23856489	The present study was designed to investigate the contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular innate immunity mediator, to the development of glomerulosclerosis in hHcys.
428	23856489	We further discovered the novel role of NOD2 in mediating Ca(2+) signaling and found that homocysteine-induced NOD2 expression enhanced transient receptor potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca(2+) release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis.
429	23856489	Moreover, we found that nephrin expression was downregulated dependently by NOD2, and overexpression of nephrin attenuated homocysteine-induced TRPC6 expression in podocytes.
430	23856489	The results add evidence to support the essential role of nephrin in mediating NOD2-induced TRPC6 expression in hHcys.
431	23856489	In conclusion, our results for the first time establish a previously unknown function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury.
432	23856489	Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated podocyte TRPC6 channels in hyperhomocysteinemia.
433	23856489	The present study was designed to investigate the contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular innate immunity mediator, to the development of glomerulosclerosis in hHcys.
434	23856489	We further discovered the novel role of NOD2 in mediating Ca(2+) signaling and found that homocysteine-induced NOD2 expression enhanced transient receptor potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca(2+) release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis.
435	23856489	Moreover, we found that nephrin expression was downregulated dependently by NOD2, and overexpression of nephrin attenuated homocysteine-induced TRPC6 expression in podocytes.
436	23856489	The results add evidence to support the essential role of nephrin in mediating NOD2-induced TRPC6 expression in hHcys.
437	23856489	In conclusion, our results for the first time establish a previously unknown function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury.
438	23856489	Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated podocyte TRPC6 channels in hyperhomocysteinemia.
439	23856489	The present study was designed to investigate the contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular innate immunity mediator, to the development of glomerulosclerosis in hHcys.
440	23856489	We further discovered the novel role of NOD2 in mediating Ca(2+) signaling and found that homocysteine-induced NOD2 expression enhanced transient receptor potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca(2+) release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis.
441	23856489	Moreover, we found that nephrin expression was downregulated dependently by NOD2, and overexpression of nephrin attenuated homocysteine-induced TRPC6 expression in podocytes.
442	23856489	The results add evidence to support the essential role of nephrin in mediating NOD2-induced TRPC6 expression in hHcys.
443	23856489	In conclusion, our results for the first time establish a previously unknown function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury.
444	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
445	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
446	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
447	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
448	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
449	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
450	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
451	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
452	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
453	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
454	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
455	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
456	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
457	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
458	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
459	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
460	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
461	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
462	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
463	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
464	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
465	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
466	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
467	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
468	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
469	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
470	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
471	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
472	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
473	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
474	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
475	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
476	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
477	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
478	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
479	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
480	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
481	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
482	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
483	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
484	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
485	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
486	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
487	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
488	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
489	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
490	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
491	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
492	23948707	NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.
493	23948707	TRPC6 channels are typically activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
494	23948707	We previously showed that podocin is required for DAG analogs to produce robust activation of TRPC6 channels in podocytes.
495	23948707	Here we show that endogenous TRPC6 channels in immortalized podocytes reciprocally coimmunoprecipitate with the catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)).
496	23948707	The NOX2-TRPC6 interaction was not detected in cells stably expressing a short hairpin RNA targeting podocin, although NOX2 and TRPC6 were present at normal levels.
497	23948707	OAG also increased steady-state surface expression of the NOX2 regulatory subunit p47(phox).
498	23948707	In whole cell recordings, TRPC6 activation by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
499	23948707	These data suggest that active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains and becomes catalytically active in response to DAG.
500	24037962	Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.
501	24037962	This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells.
502	24037962	These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling.
503	24037962	Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI).
504	24037962	These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes.
505	24037962	Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.
506	24037962	This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells.
507	24037962	These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling.
508	24037962	Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI).
509	24037962	These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes.
510	24037962	Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.
511	24037962	This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells.
512	24037962	These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling.
513	24037962	Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI).
514	24037962	These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes.
515	24037962	Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.
516	24037962	This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells.
517	24037962	These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling.
518	24037962	Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI).
519	24037962	These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes.
520	24194522	Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates.
521	24194522	Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression.
522	24194522	Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates.
523	24194522	Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression.
524	24196483	Here we improved ELV isolation protocols employing density centrifugation to remove THP and albumin, and isolated a glomerular membranous vesicle (GMV)-enriched subfraction from 7 individuals identifying 1830 proteins and in 3 patients with glomerular disease identifying 5657 unique proteins.
525	24196483	We show many nephrotic syndrome proteins, proteases, and complement proteins involved in glomerular disease are in GMVs and some were only shed in the disease state (nephrin, TRPC6, INF2 and phospholipase A2 receptor).
526	24598806	Coexpression of TRPC6-N143S with wild-type TRPC6 or TRPC3 channels did not alter stretch-evoked responses compared with when TRPC3 channels were expressed by themselves, indicating that TRPC6-N143S does not function as a dominant-negative.
527	24646854	Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
528	24646854	Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux.
529	24646854	Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis.
530	24646854	Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability.
531	24646854	Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli.
532	24646854	Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
533	24646854	Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
534	24646854	Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux.
535	24646854	Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis.
536	24646854	Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability.
537	24646854	Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli.
538	24646854	Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
539	24646854	Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
540	24646854	Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux.
541	24646854	Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis.
542	24646854	Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability.
543	24646854	Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli.
544	24646854	Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
545	24646854	Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
546	24646854	Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux.
547	24646854	Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis.
548	24646854	Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability.
549	24646854	Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli.
550	24646854	Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
551	24646854	Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
552	24646854	Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux.
553	24646854	Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis.
554	24646854	Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability.
555	24646854	Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli.
556	24646854	Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
557	24646854	Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
558	24646854	Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux.
559	24646854	Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis.
560	24646854	Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability.
561	24646854	Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli.
562	24646854	Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
563	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
564	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
565	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
566	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
567	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
568	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
569	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
570	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
571	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
572	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
573	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
574	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
575	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
576	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
577	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
578	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
579	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
580	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
581	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
582	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
583	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
584	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
585	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
586	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
587	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
588	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
589	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
590	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
591	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
592	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
593	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
594	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
595	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
596	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
597	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
598	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
599	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
600	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
601	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
602	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
603	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
604	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
605	24731445	Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.
606	24731445	We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent.
607	24731445	High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered.
608	24731445	AngII and inducing podocyte injury also specifically increased TRPC6 expression.
609	24731445	Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression.
610	24731445	These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
611	24731445	Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
612	24740790	The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function.
613	24740790	TRPC6 was phosphorylated at Thr(69) in nonstimulated podocytes, but this declined upon ANG II stimulation or overexpression of constitutively active calcineurin phosphatase.
614	24740790	ANG II induced podocyte motility in an in vitro wound assay, and this was reduced 30-60% in cells overexpressing a phosphomimetic mutant TRPC6 (TRPC6T70E/S322E) or activated PKG (P < 0.05).
615	24740790	Pretreatment of podocytes with the PKG agonists S-nitroso-N-acetyl-dl-penicillamine (nitric oxide donor), 8-bromo-cGMP, Bay 41-2772 (soluble guanylate cyclase activator), or phosphodiesterase 5 (PDE5) inhibitor 4-{[3',4'-(methylenedioxy)benzyl]amino}[7]-6-methoxyquinazoline attenuated ANG II-induced Thr(69) dephosphorylation and also inhibited TRPC6-dependent podocyte motility by 30-60%.
616	24740790	These data reveal that PKG activation strategies, including PDE5 inhibition, ameliorate ANG II-induced podocyte dysmotility by targeting TRPC6 in podocytes, highlighting the potential therapeutic utility of these approaches to treat hyperactive TRPC6-dependent glomerular disease.
617	24740790	The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function.
618	24740790	TRPC6 was phosphorylated at Thr(69) in nonstimulated podocytes, but this declined upon ANG II stimulation or overexpression of constitutively active calcineurin phosphatase.
619	24740790	ANG II induced podocyte motility in an in vitro wound assay, and this was reduced 30-60% in cells overexpressing a phosphomimetic mutant TRPC6 (TRPC6T70E/S322E) or activated PKG (P < 0.05).
620	24740790	Pretreatment of podocytes with the PKG agonists S-nitroso-N-acetyl-dl-penicillamine (nitric oxide donor), 8-bromo-cGMP, Bay 41-2772 (soluble guanylate cyclase activator), or phosphodiesterase 5 (PDE5) inhibitor 4-{[3',4'-(methylenedioxy)benzyl]amino}[7]-6-methoxyquinazoline attenuated ANG II-induced Thr(69) dephosphorylation and also inhibited TRPC6-dependent podocyte motility by 30-60%.
621	24740790	These data reveal that PKG activation strategies, including PDE5 inhibition, ameliorate ANG II-induced podocyte dysmotility by targeting TRPC6 in podocytes, highlighting the potential therapeutic utility of these approaches to treat hyperactive TRPC6-dependent glomerular disease.
622	24740790	The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function.
623	24740790	TRPC6 was phosphorylated at Thr(69) in nonstimulated podocytes, but this declined upon ANG II stimulation or overexpression of constitutively active calcineurin phosphatase.
624	24740790	ANG II induced podocyte motility in an in vitro wound assay, and this was reduced 30-60% in cells overexpressing a phosphomimetic mutant TRPC6 (TRPC6T70E/S322E) or activated PKG (P < 0.05).
625	24740790	Pretreatment of podocytes with the PKG agonists S-nitroso-N-acetyl-dl-penicillamine (nitric oxide donor), 8-bromo-cGMP, Bay 41-2772 (soluble guanylate cyclase activator), or phosphodiesterase 5 (PDE5) inhibitor 4-{[3',4'-(methylenedioxy)benzyl]amino}[7]-6-methoxyquinazoline attenuated ANG II-induced Thr(69) dephosphorylation and also inhibited TRPC6-dependent podocyte motility by 30-60%.
626	24740790	These data reveal that PKG activation strategies, including PDE5 inhibition, ameliorate ANG II-induced podocyte dysmotility by targeting TRPC6 in podocytes, highlighting the potential therapeutic utility of these approaches to treat hyperactive TRPC6-dependent glomerular disease.
627	24740790	The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function.
628	24740790	TRPC6 was phosphorylated at Thr(69) in nonstimulated podocytes, but this declined upon ANG II stimulation or overexpression of constitutively active calcineurin phosphatase.
629	24740790	ANG II induced podocyte motility in an in vitro wound assay, and this was reduced 30-60% in cells overexpressing a phosphomimetic mutant TRPC6 (TRPC6T70E/S322E) or activated PKG (P < 0.05).
630	24740790	Pretreatment of podocytes with the PKG agonists S-nitroso-N-acetyl-dl-penicillamine (nitric oxide donor), 8-bromo-cGMP, Bay 41-2772 (soluble guanylate cyclase activator), or phosphodiesterase 5 (PDE5) inhibitor 4-{[3',4'-(methylenedioxy)benzyl]amino}[7]-6-methoxyquinazoline attenuated ANG II-induced Thr(69) dephosphorylation and also inhibited TRPC6-dependent podocyte motility by 30-60%.
631	24740790	These data reveal that PKG activation strategies, including PDE5 inhibition, ameliorate ANG II-induced podocyte dysmotility by targeting TRPC6 in podocytes, highlighting the potential therapeutic utility of these approaches to treat hyperactive TRPC6-dependent glomerular disease.
632	24740790	The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function.
633	24740790	TRPC6 was phosphorylated at Thr(69) in nonstimulated podocytes, but this declined upon ANG II stimulation or overexpression of constitutively active calcineurin phosphatase.
634	24740790	ANG II induced podocyte motility in an in vitro wound assay, and this was reduced 30-60% in cells overexpressing a phosphomimetic mutant TRPC6 (TRPC6T70E/S322E) or activated PKG (P < 0.05).
635	24740790	Pretreatment of podocytes with the PKG agonists S-nitroso-N-acetyl-dl-penicillamine (nitric oxide donor), 8-bromo-cGMP, Bay 41-2772 (soluble guanylate cyclase activator), or phosphodiesterase 5 (PDE5) inhibitor 4-{[3',4'-(methylenedioxy)benzyl]amino}[7]-6-methoxyquinazoline attenuated ANG II-induced Thr(69) dephosphorylation and also inhibited TRPC6-dependent podocyte motility by 30-60%.
636	24740790	These data reveal that PKG activation strategies, including PDE5 inhibition, ameliorate ANG II-induced podocyte dysmotility by targeting TRPC6 in podocytes, highlighting the potential therapeutic utility of these approaches to treat hyperactive TRPC6-dependent glomerular disease.
637	24942878	Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes.
638	24942878	TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay.
639	24942878	High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression.
640	24942878	Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression.
641	24942878	High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.
642	24942878	Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes.
643	24942878	TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay.
644	24942878	High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression.
645	24942878	Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression.
646	24942878	High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.
647	24942878	Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes.
648	24942878	TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay.
649	24942878	High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression.
650	24942878	Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression.
651	24942878	High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.
652	24942878	Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes.
653	24942878	TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay.
654	24942878	High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression.
655	24942878	Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression.
656	24942878	High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.
657	24942878	Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes.
658	24942878	TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay.
659	24942878	High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression.
660	24942878	Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression.
661	24942878	High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.
662	25393730	Transient receptor potential cation channel 6 (TRPC6) is a nonselective cation channel, and abnormal expression and gain of function of TRPC6 are involved in the pathogenesis of hereditary and nonhereditary forms of renal disease.
663	25393730	We aimed to examine the effect of the mammalian target of rapamycin (mTOR) complex (mTOR complex 1 [mTORC1] or mTOR complex 2 [mTORC2]) signaling pathways on TRPC6 in podocytes, which are highly terminally differentiated renal epithelial cells that are critically required for the maintenance of the glomerular filtration barrier.
664	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
665	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
666	25393730	These findings indicate that the mTORC2 signaling pathway regulates TRPC6 in podocytes but that the mTORC1 signaling pathway does not appear to exert an effect on TRPC6.
667	25393730	Transient receptor potential cation channel 6 (TRPC6) is a nonselective cation channel, and abnormal expression and gain of function of TRPC6 are involved in the pathogenesis of hereditary and nonhereditary forms of renal disease.
668	25393730	We aimed to examine the effect of the mammalian target of rapamycin (mTOR) complex (mTOR complex 1 [mTORC1] or mTOR complex 2 [mTORC2]) signaling pathways on TRPC6 in podocytes, which are highly terminally differentiated renal epithelial cells that are critically required for the maintenance of the glomerular filtration barrier.
669	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
670	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
671	25393730	These findings indicate that the mTORC2 signaling pathway regulates TRPC6 in podocytes but that the mTORC1 signaling pathway does not appear to exert an effect on TRPC6.
672	25393730	Transient receptor potential cation channel 6 (TRPC6) is a nonselective cation channel, and abnormal expression and gain of function of TRPC6 are involved in the pathogenesis of hereditary and nonhereditary forms of renal disease.
673	25393730	We aimed to examine the effect of the mammalian target of rapamycin (mTOR) complex (mTOR complex 1 [mTORC1] or mTOR complex 2 [mTORC2]) signaling pathways on TRPC6 in podocytes, which are highly terminally differentiated renal epithelial cells that are critically required for the maintenance of the glomerular filtration barrier.
674	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
675	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
676	25393730	These findings indicate that the mTORC2 signaling pathway regulates TRPC6 in podocytes but that the mTORC1 signaling pathway does not appear to exert an effect on TRPC6.
677	25521631	Phospholipase C epsilon (PLCε) induced TRPC6 activation: a common but redundant mechanism in primary podocytes.
678	25521631	In eukaryotic cells, activation of phospholipase C (PLC)-coupled membrane receptors by hormones leads to an increase in the intracellular Ca(2+) concentration [Ca(2+) ]i .
679	25521631	Catalytic activity of PLCs results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) which opens DAG-sensitive classical transient receptor channels 3, 6, and 7 (TRPC3/6/7), initiating Ca(2+) influx from the extracellular space.
680	25521631	PLCε-/- podocytes however, were undistinguishable from WT podocytes in their angiotensin II-induced formation of actin stress fibers and their GTPγS-induced TRPC6 activation, pointing to a redundant role of PLCε-mediated TRPC6 activation at least in podocytes.
681	25521631	Phospholipase C epsilon (PLCε) induced TRPC6 activation: a common but redundant mechanism in primary podocytes.
682	25521631	In eukaryotic cells, activation of phospholipase C (PLC)-coupled membrane receptors by hormones leads to an increase in the intracellular Ca(2+) concentration [Ca(2+) ]i .
683	25521631	Catalytic activity of PLCs results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) which opens DAG-sensitive classical transient receptor channels 3, 6, and 7 (TRPC3/6/7), initiating Ca(2+) influx from the extracellular space.
684	25521631	PLCε-/- podocytes however, were undistinguishable from WT podocytes in their angiotensin II-induced formation of actin stress fibers and their GTPγS-induced TRPC6 activation, pointing to a redundant role of PLCε-mediated TRPC6 activation at least in podocytes.
685	26017975	Exposure of podocytes to TNF increased phosphorylation of NF-κB p65-RelA followed by increased tyrosine phosphorylation of STAT3.
686	26017975	STAT3 activation was blocked by the NF-κB inhibitor JSH-23 and by the STAT3 inhibitor stattic, whereas TNF-evoked NF-κB activation was not affected by stattic.
687	26017975	TNF treatment increased nuclear accumulation of nuclear factor of activated T cells (NFAT)c1 in podocytes, a process that occurred downstream of STAT3 activation.
688	26017975	TNF also increased expression of cyclin D1 but had no effect on cyclin-dependent kinase 4, p27(kip), or podocin.
689	26017975	Despite its effects on cyclin D1, TNF treatment for up to 72 h did not cause podocytes to reenter the cell cycle.
690	26017975	TNF increased total expression of transient receptor potential (TRP)C6 channels through a pathway dependent on NFATc1 and increased the steady-state expression of TRPC6 subunits on the podocyte cell surface.
691	26017975	TNF effects on TRPC6 trafficking required ROS.
692	26017975	The effects of TNF on NFATc1 and TRPC6 expression were blocked by cyclosporine A but were not blocked by the pan-TRP inhibitor SKF-96365.
693	26017975	Exposure of podocytes to TNF increased phosphorylation of NF-κB p65-RelA followed by increased tyrosine phosphorylation of STAT3.
694	26017975	STAT3 activation was blocked by the NF-κB inhibitor JSH-23 and by the STAT3 inhibitor stattic, whereas TNF-evoked NF-κB activation was not affected by stattic.
695	26017975	TNF treatment increased nuclear accumulation of nuclear factor of activated T cells (NFAT)c1 in podocytes, a process that occurred downstream of STAT3 activation.
696	26017975	TNF also increased expression of cyclin D1 but had no effect on cyclin-dependent kinase 4, p27(kip), or podocin.
697	26017975	Despite its effects on cyclin D1, TNF treatment for up to 72 h did not cause podocytes to reenter the cell cycle.
698	26017975	TNF increased total expression of transient receptor potential (TRP)C6 channels through a pathway dependent on NFATc1 and increased the steady-state expression of TRPC6 subunits on the podocyte cell surface.
699	26017975	TNF effects on TRPC6 trafficking required ROS.
700	26017975	The effects of TNF on NFATc1 and TRPC6 expression were blocked by cyclosporine A but were not blocked by the pan-TRP inhibitor SKF-96365.
701	26017975	Exposure of podocytes to TNF increased phosphorylation of NF-κB p65-RelA followed by increased tyrosine phosphorylation of STAT3.
702	26017975	STAT3 activation was blocked by the NF-κB inhibitor JSH-23 and by the STAT3 inhibitor stattic, whereas TNF-evoked NF-κB activation was not affected by stattic.
703	26017975	TNF treatment increased nuclear accumulation of nuclear factor of activated T cells (NFAT)c1 in podocytes, a process that occurred downstream of STAT3 activation.
704	26017975	TNF also increased expression of cyclin D1 but had no effect on cyclin-dependent kinase 4, p27(kip), or podocin.
705	26017975	Despite its effects on cyclin D1, TNF treatment for up to 72 h did not cause podocytes to reenter the cell cycle.
706	26017975	TNF increased total expression of transient receptor potential (TRP)C6 channels through a pathway dependent on NFATc1 and increased the steady-state expression of TRPC6 subunits on the podocyte cell surface.
707	26017975	TNF effects on TRPC6 trafficking required ROS.
708	26017975	The effects of TNF on NFATc1 and TRPC6 expression were blocked by cyclosporine A but were not blocked by the pan-TRP inhibitor SKF-96365.
709	26147534	Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis.
710	26147534	Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism.
711	26147534	When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.
712	26147534	Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis.
713	26147534	Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism.
714	26147534	When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.
715	26147534	Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis.
716	26147534	Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism.
717	26147534	When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.
718	26156092	Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 and INF2.
719	26160898	The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes.
720	26160898	However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365.
721	26160898	Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton.
722	26160898	The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes.
723	26160898	However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365.
724	26160898	Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton.
725	26404773	Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes.
726	26404773	Therefore, in this study, we aimed at defining how the protein kinase C (PKC) system, one of the key intracellular signalling pathways, regulates TRPC6 function and expression.
727	26404773	Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes.
728	26404773	Therefore, in this study, we aimed at defining how the protein kinase C (PKC) system, one of the key intracellular signalling pathways, regulates TRPC6 function and expression.
729	26436650	Here, we showed that critical components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s).
730	26436650	In cultured podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and calcineurin activity.
731	26436650	Moreover, NFATC3 nuclear translocation, synaptopodin degradation, integrin β3 (ITGB3) activation, and actin fiber loss, which are downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but blocked by the calcineurin inhibitor FK506.
732	26436650	Here, we showed that critical components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s).
733	26436650	In cultured podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and calcineurin activity.
734	26436650	Moreover, NFATC3 nuclear translocation, synaptopodin degradation, integrin β3 (ITGB3) activation, and actin fiber loss, which are downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but blocked by the calcineurin inhibitor FK506.
735	26490951	The identification of the two Ca(2+) permeant channels TRPC5 and TRPC6 as mediators of this pathway not only bolstered the importance of podocyte cytoskeleton dynamics but also revealed promising drug targets for treatment-resistant nephrotic syndrome.
736	26656101	Angiotensin II (Ang II) levels are found to be elevated in diabetes; furthermore, it was reported that Ang II causes activation of TRPC6 in podocytes.
737	26823720	The urinary albumin (UAL), creatinine clearance rate (Ccr) and major biochemical parameters, including glucose, insulin, serum creatinine (Scr), urea nitrogen, total cholesterol (CHO) and triglyceride (TG), were examined 12 weeks after the administration of FK506.
738	26823720	The expressions of the canonical transient receptor potential 6 (TRPC6), nuclear factor of activated T-cells (NFAT) and nephrin were detected by Western blotting and qPCR.
739	26823720	In cell experiments, FK506 improved the decreased expression of nephrin and suppressed the elevated expression of both TRPC6 and NFAT caused by high glucose in accordance with TRPC6 blocker U73122.
740	26823720	The urinary albumin (UAL), creatinine clearance rate (Ccr) and major biochemical parameters, including glucose, insulin, serum creatinine (Scr), urea nitrogen, total cholesterol (CHO) and triglyceride (TG), were examined 12 weeks after the administration of FK506.
741	26823720	The expressions of the canonical transient receptor potential 6 (TRPC6), nuclear factor of activated T-cells (NFAT) and nephrin were detected by Western blotting and qPCR.
742	26823720	In cell experiments, FK506 improved the decreased expression of nephrin and suppressed the elevated expression of both TRPC6 and NFAT caused by high glucose in accordance with TRPC6 blocker U73122.
743	26892346	We then characterized 19 human FSGS-related TRPC6 mutations, the majority of which caused gain-of-function mutations.
744	26940093	Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte-specific transient receptor potential cation channel, subfamily C, member 6.
745	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
746	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
747	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
748	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
749	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
750	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
751	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
752	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
753	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
754	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
755	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
756	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
757	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
758	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
759	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
760	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
761	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
762	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
763	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
764	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
765	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
766	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
767	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
768	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
769	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
770	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
771	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
772	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
773	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
774	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
775	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
776	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
777	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
778	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
779	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
780	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
781	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
782	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
783	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
784	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
785	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
786	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
787	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
788	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
789	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
790	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
791	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
792	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
793	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
794	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
795	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
796	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
797	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
798	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
799	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
800	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
801	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
802	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
803	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
804	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
805	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
806	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
807	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
808	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
809	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
810	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
811	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
812	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
813	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
814	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
815	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
816	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
817	27020855	Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria.
818	27020855	Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6.
819	27020855	We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes.
820	27020855	Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it.
821	27020855	Mechanistically, synaptopodin-dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons.
822	27020855	Overexpression of wild-type or FSGS-inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6-mediated calcium influx and induced apoptosis.
823	27020855	In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6.
824	27020855	Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice.
825	27020855	Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction.
826	27109610	Apoptosis, cell viability, expression of TRPC6, nuclear factor of activated T cells (NFAT2) and B‑cell lymphoma 2‑associated X protein (Bax), as well as the intracellular Ca2+ concentration were subsequently analyzed.
827	27109610	Furthermore, enhanced NFAT2 and Bax expression was detected.
828	27109610	AS‑IV also suppressed NFAT2 and Bax expression.
829	27151926	Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in Podocytes.
830	27151926	Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca²⁺ influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel.
831	27151926	Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells.
832	27151926	Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria.
833	27151926	Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in Podocytes.
834	27151926	Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca²⁺ influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel.
835	27151926	Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells.
836	27151926	Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria.
837	27151926	Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in Podocytes.
838	27151926	Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca²⁺ influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel.
839	27151926	Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells.
840	27151926	Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria.
841	27153922	Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice.
842	27630573	TRPC6 activation by 20-HETE was eliminated in cells pretreated with TEMPOL, a membrane-permeable superoxide dismutase mimic.
843	27630573	Responses to 20-HETE were eliminated by siRNA knockdown of podocin, a protein that organizes NADPH oxidase complexes with TRPC6 subunits in this cell type.
844	27630573	TRPC6 activation by 20-HETE was eliminated in cells pretreated with TEMPOL, a membrane-permeable superoxide dismutase mimic.
845	27630573	Responses to 20-HETE were eliminated by siRNA knockdown of podocin, a protein that organizes NADPH oxidase complexes with TRPC6 subunits in this cell type.
846	27895156	Sildenafil Prevents Podocyte Injury via PPAR-γ-Mediated TRPC6 Inhibition.
847	27895156	We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria.
848	27895156	Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP.
849	27895156	Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter.
850	27895156	Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil.
851	27895156	Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity.
852	27895156	Sildenafil Prevents Podocyte Injury via PPAR-γ-Mediated TRPC6 Inhibition.
853	27895156	We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria.
854	27895156	Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP.
855	27895156	Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter.
856	27895156	Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil.
857	27895156	Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity.
858	27895156	Sildenafil Prevents Podocyte Injury via PPAR-γ-Mediated TRPC6 Inhibition.
859	27895156	We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria.
860	27895156	Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP.
861	27895156	Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter.
862	27895156	Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil.
863	27895156	Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity.
864	27895156	Sildenafil Prevents Podocyte Injury via PPAR-γ-Mediated TRPC6 Inhibition.
865	27895156	We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria.
866	27895156	Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP.
867	27895156	Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter.
868	27895156	Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil.
869	27895156	Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity.
870	27895156	Sildenafil Prevents Podocyte Injury via PPAR-γ-Mediated TRPC6 Inhibition.
871	27895156	We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria.
872	27895156	Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP.
873	27895156	Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter.
874	27895156	Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil.
875	27895156	Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity.
876	27895156	Sildenafil Prevents Podocyte Injury via PPAR-γ-Mediated TRPC6 Inhibition.
877	27895156	We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria.
878	27895156	Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP.
879	27895156	Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter.
880	27895156	Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil.
881	27895156	Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity.
882	28028935	Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2.
883	28028935	TRP melastatin (TRPM2) non-selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology.
884	28028935	Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown.
885	28028935	In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.
886	28028935	Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2.
887	28028935	TRP melastatin (TRPM2) non-selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology.
888	28028935	Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown.
889	28028935	In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.
890	28028935	Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2.
891	28028935	TRP melastatin (TRPM2) non-selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology.
892	28028935	Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown.
893	28028935	In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.
894	28331185	Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca²⁺ flux in podocytes.
895	28331185	Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.
896	28331185	Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca²⁺ flux in podocytes.
897	28331185	Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.
898	28442546	Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling.
899	28442546	Functional experiments based on the ability of Klotho to down-regulate TRPC6 channel activity confirm the importance of these residues.
900	28442546	Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling.
901	28442546	Functional experiments based on the ability of Klotho to down-regulate TRPC6 channel activity confirm the importance of these residues.
902	28629718	Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca²⁺-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains.
903	28629718	Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus.
904	28629718	Most but not all of the recurrent FSGS plasma samples that we examined also caused a loss of podocin over a period of several hours.
905	28629718	The loss of podocin was also seen following exposure to suPAR but not TNF.
906	28629718	However, TNF increased the effects of suPAR on TRPC6 and podocin, and TNF and suPAR are required for the full effects of one of the recurrent FSGS plasma samples.
907	28629718	The actions of FSGS plasma, suPAR and TNF on surface abundance of TRPC6 were blocked by cilengitide, an inhibitor of αvβ3-integrin signaling.
908	28629718	These data suggest that primary FSGS is a heterogeneous condition mediated by multiple circulating factors, and support TRPC6 and αvβ3-integrin as potential therapeutic targets.
909	28629718	Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca²⁺-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains.
910	28629718	Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus.
911	28629718	Most but not all of the recurrent FSGS plasma samples that we examined also caused a loss of podocin over a period of several hours.
912	28629718	The loss of podocin was also seen following exposure to suPAR but not TNF.
913	28629718	However, TNF increased the effects of suPAR on TRPC6 and podocin, and TNF and suPAR are required for the full effects of one of the recurrent FSGS plasma samples.
914	28629718	The actions of FSGS plasma, suPAR and TNF on surface abundance of TRPC6 were blocked by cilengitide, an inhibitor of αvβ3-integrin signaling.
915	28629718	These data suggest that primary FSGS is a heterogeneous condition mediated by multiple circulating factors, and support TRPC6 and αvβ3-integrin as potential therapeutic targets.
916	28629718	Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca²⁺-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains.
917	28629718	Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus.
918	28629718	Most but not all of the recurrent FSGS plasma samples that we examined also caused a loss of podocin over a period of several hours.
919	28629718	The loss of podocin was also seen following exposure to suPAR but not TNF.
920	28629718	However, TNF increased the effects of suPAR on TRPC6 and podocin, and TNF and suPAR are required for the full effects of one of the recurrent FSGS plasma samples.
921	28629718	The actions of FSGS plasma, suPAR and TNF on surface abundance of TRPC6 were blocked by cilengitide, an inhibitor of αvβ3-integrin signaling.
922	28629718	These data suggest that primary FSGS is a heterogeneous condition mediated by multiple circulating factors, and support TRPC6 and αvβ3-integrin as potential therapeutic targets.
923	28629718	Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca²⁺-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains.
924	28629718	Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus.
925	28629718	Most but not all of the recurrent FSGS plasma samples that we examined also caused a loss of podocin over a period of several hours.
926	28629718	The loss of podocin was also seen following exposure to suPAR but not TNF.
927	28629718	However, TNF increased the effects of suPAR on TRPC6 and podocin, and TNF and suPAR are required for the full effects of one of the recurrent FSGS plasma samples.
928	28629718	The actions of FSGS plasma, suPAR and TNF on surface abundance of TRPC6 were blocked by cilengitide, an inhibitor of αvβ3-integrin signaling.
929	28629718	These data suggest that primary FSGS is a heterogeneous condition mediated by multiple circulating factors, and support TRPC6 and αvβ3-integrin as potential therapeutic targets.
930	28629718	Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca²⁺-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains.
931	28629718	Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus.
932	28629718	Most but not all of the recurrent FSGS plasma samples that we examined also caused a loss of podocin over a period of several hours.
933	28629718	The loss of podocin was also seen following exposure to suPAR but not TNF.
934	28629718	However, TNF increased the effects of suPAR on TRPC6 and podocin, and TNF and suPAR are required for the full effects of one of the recurrent FSGS plasma samples.
935	28629718	The actions of FSGS plasma, suPAR and TNF on surface abundance of TRPC6 were blocked by cilengitide, an inhibitor of αvβ3-integrin signaling.
936	28629718	These data suggest that primary FSGS is a heterogeneous condition mediated by multiple circulating factors, and support TRPC6 and αvβ3-integrin as potential therapeutic targets.
937	28687864	The cation channels P2X4 and TRPC6 were shown to be involved in mechanosignaling in podocytes.
938	28687864	Downstream of mechanosensors, experimental evidence suggests the involvement of MAP kinases, Ca²⁺ and COX2 in mechanosignaling and an emerging role of YAP/TAZ.
939	28877958	We confirmed serine 14 as a target of MAPKs and proline-directed kinases like cyclin-dependent kinase 5 (Cdk5) in cell-based as well as in vitro kinase assays and quantitative phosphoproteomic analysis of TRPC6.
940	28916337	The patch-clamp experiments indicated that Ang II increased the current of transient receptor potential canonical 6 (TRPC6).
941	28916337	Western blot assay presented that Ang II obviously elevated LC3-II/LC3-I ratio and expression of beclin-1, and reduced expression of P62.
942	28916337	Consequently, this study demonstrated that Ang II could increase TRPC6 induced Ca²⁺ influx and enhance autophagy through increasing ROS levels in podocytes, and autophagy could protect Ang II-treated podocytes.
943	28916337	Improving TRPC6 channels and autophagy may become a new targeted therapy to relieve glomerular damage induced by Ang II.
944	28916337	The patch-clamp experiments indicated that Ang II increased the current of transient receptor potential canonical 6 (TRPC6).
945	28916337	Western blot assay presented that Ang II obviously elevated LC3-II/LC3-I ratio and expression of beclin-1, and reduced expression of P62.
946	28916337	Consequently, this study demonstrated that Ang II could increase TRPC6 induced Ca²⁺ influx and enhance autophagy through increasing ROS levels in podocytes, and autophagy could protect Ang II-treated podocytes.
947	28916337	Improving TRPC6 channels and autophagy may become a new targeted therapy to relieve glomerular damage induced by Ang II.
948	28916337	The patch-clamp experiments indicated that Ang II increased the current of transient receptor potential canonical 6 (TRPC6).
949	28916337	Western blot assay presented that Ang II obviously elevated LC3-II/LC3-I ratio and expression of beclin-1, and reduced expression of P62.
950	28916337	Consequently, this study demonstrated that Ang II could increase TRPC6 induced Ca²⁺ influx and enhance autophagy through increasing ROS levels in podocytes, and autophagy could protect Ang II-treated podocytes.
951	28916337	Improving TRPC6 channels and autophagy may become a new targeted therapy to relieve glomerular damage induced by Ang II.
952	29138824	However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes.
953	29138824	Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH).
954	29138824	Genomic DNA of the siblings affected by FH with biopsy‑proven FSGS was analyzed, and their father was screened for 18 gene mutations associated with FSGS [nephrin, podocin, CD2 associated protein, phospholipase C ε, actinin α 4, transient receptor potential cation channel subfamily C member 6, inverted formin, FH2 and WH2 domain containing, Wilms tumor 1, LIM homeobox transcription factor 1 β, laminin subunit β 2, laminin subunit β 3, galactosida α, integrin subunit β 4, scavenger receptor class B member 2, coenzyme Q2, decaprenyl diphosphate synthase subunit 2, mitochondrially encoded tRNA leucine 1 (UUA/G; TRNL1) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1] using matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry technology.
955	29138824	Using mass array technology, a TRNL1 missense homozygous mutation (m. 3290T>C) was identified in the probands diagnosed with FH and manifested as FSGS on biopsy.
956	29138824	In the present study, a mutation in TRNL1 (m. 3290T>C) was identified, which was the first reported variant associated with FSGS.
957	29138824	The COL4A4 (c. 4195A>T) may co‑segregate with FSGS.
958	29207011	In iatrogenic hyperinsulinemic rat renal tissues, malondialdehyde, interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α), type IV collagen and laminin levels were increased, whereas glutathione peroxidase and superoxide dismutase activity levels were decreased.
959	29207011	Nicotinamide adenine dinucleotide phosphate oxidase 4 expression and extracellular signal‑regulated kinase 1/2 (ERK1/2) activation were upregulated, and canonical transient receptor potential cation channel 6 (TRPC6) protein expression was downregulated.
960	29207011	These findings suggested that AS‑IV prevented rat kidney injury caused by iatrogenic hyperinsulinemia by inhibiting oxidative stress, IL‑1β and TNF‑α overproduction, downregulating ERK1/2 activation, and upregulating TRPC6 expression.
961	29207011	In iatrogenic hyperinsulinemic rat renal tissues, malondialdehyde, interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α), type IV collagen and laminin levels were increased, whereas glutathione peroxidase and superoxide dismutase activity levels were decreased.
962	29207011	Nicotinamide adenine dinucleotide phosphate oxidase 4 expression and extracellular signal‑regulated kinase 1/2 (ERK1/2) activation were upregulated, and canonical transient receptor potential cation channel 6 (TRPC6) protein expression was downregulated.
963	29207011	These findings suggested that AS‑IV prevented rat kidney injury caused by iatrogenic hyperinsulinemia by inhibiting oxidative stress, IL‑1β and TNF‑α overproduction, downregulating ERK1/2 activation, and upregulating TRPC6 expression.
964	29312514	TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitial damage and renal fibrosis in obstructed kidneys.
965	29312514	In addition, we observed decreased expression of anti-apoptotic Bcl2 and increased expression of pro-apoptotic cleaved caspase 3 in WT diabetic mice, but such changes were not significant in TRPC3/6/7^-/- diabetic mice.
966	29312514	Western blot and immunohistochemistry revealed that TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of these signaling molecules was not changed in TRPC3/6/7^-/- diabetic mice.
967	29335087	Transient receptor potential cation channel 6 (TRPC6) is a member of the transient receptor superfamily encoded by the TRPC6 gene and is widely expressed in tissues and organs of the human body, especially in the glomerular podocytes.
968	29335087	TRPC6 interacts with various slit diaphragm (SD) proteins including podocin, nephrin, ACTN4, and CD2AP to maintain the normal structure and function of glomerular podocytes.
969	29335087	Transient receptor potential cation channel 6 (TRPC6) is a member of the transient receptor superfamily encoded by the TRPC6 gene and is widely expressed in tissues and organs of the human body, especially in the glomerular podocytes.
970	29335087	TRPC6 interacts with various slit diaphragm (SD) proteins including podocin, nephrin, ACTN4, and CD2AP to maintain the normal structure and function of glomerular podocytes.
971	29556761	A third group of animal models involves genetic engineering techniques targeting podocyte expression molecules, such as podocin, CD2-associated protein, and TRPC6 channels.
972	29643035	[Correlation between expressions of VEGF and TRPC6 and their roles in podocyte injury in rats with diabetic nephropathy].
973	29793963	A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease.
974	29793963	Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SS^Nox4-/-) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6.
975	29793963	Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.
976	29793963	A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease.
977	29793963	Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SS^Nox4-/-) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6.
978	29793963	Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.
979	29793963	A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease.
980	29793963	Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SS^Nox4-/-) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6.
981	29793963	Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.
982	30255020	In this review, we will focus on slit diaphragm proteins such as nephrin, podocin, TRPC6/5, as well as cytoskeletal proteins Rho/small GTPases and synaptopodin and their respective roles in participating in the pathogenesis of proteinuric kidney diseases.
983	30664212	Participation of the AngII/TRPC6/NFAT axis in the pathogenesis of podocyte injury in rats with type 2 diabetes.
984	30664212	Angiotensin II (AngII) has been revealed to enhance TRPC6 currents in certain types of cells, including podocytes and ventricular myocytes.
985	30664212	There was increased expression of AngII and TRPC6 in diabetic rats.
986	30664212	Taken together, the present results suggested that the AngII/TRPC6/NFAT axis may be a crucial signaling pathway in podocytes that is necessary for maintaining the integrity of the glomerular filtration barrier.
987	30664212	Participation of the AngII/TRPC6/NFAT axis in the pathogenesis of podocyte injury in rats with type 2 diabetes.
988	30664212	Angiotensin II (AngII) has been revealed to enhance TRPC6 currents in certain types of cells, including podocytes and ventricular myocytes.
989	30664212	There was increased expression of AngII and TRPC6 in diabetic rats.
990	30664212	Taken together, the present results suggested that the AngII/TRPC6/NFAT axis may be a crucial signaling pathway in podocytes that is necessary for maintaining the integrity of the glomerular filtration barrier.
991	30664212	Participation of the AngII/TRPC6/NFAT axis in the pathogenesis of podocyte injury in rats with type 2 diabetes.
992	30664212	Angiotensin II (AngII) has been revealed to enhance TRPC6 currents in certain types of cells, including podocytes and ventricular myocytes.
993	30664212	There was increased expression of AngII and TRPC6 in diabetic rats.
994	30664212	Taken together, the present results suggested that the AngII/TRPC6/NFAT axis may be a crucial signaling pathway in podocytes that is necessary for maintaining the integrity of the glomerular filtration barrier.
995	30664212	Participation of the AngII/TRPC6/NFAT axis in the pathogenesis of podocyte injury in rats with type 2 diabetes.
996	30664212	Angiotensin II (AngII) has been revealed to enhance TRPC6 currents in certain types of cells, including podocytes and ventricular myocytes.
997	30664212	There was increased expression of AngII and TRPC6 in diabetic rats.
998	30664212	Taken together, the present results suggested that the AngII/TRPC6/NFAT axis may be a crucial signaling pathway in podocytes that is necessary for maintaining the integrity of the glomerular filtration barrier.
999	30782481	Group I metabotropic glutamate receptor activation induces TRPC6-dependent calcium influx and RhoA activation in cultured human kidney podocytes.
1000	30782481	Additionally, nonselective inhibitors of TRPC or TRPC6 knockdown clearly inhibited RhoA activation induced by DHPG, as assessed by Glutathione-S-transferase pull-down assay followed by Western blotting.
1001	30782481	Group I metabotropic glutamate receptor activation induces TRPC6-dependent calcium influx and RhoA activation in cultured human kidney podocytes.
1002	30782481	Additionally, nonselective inhibitors of TRPC or TRPC6 knockdown clearly inhibited RhoA activation induced by DHPG, as assessed by Glutathione-S-transferase pull-down assay followed by Western blotting.
1003	30953689	TRPC6 can form a functional heteromultimer with TRPC3, and it has been suggested that TRPC5 may also play a role in glomerular disease progression, although the evidence on this is contradictory.
1004	30953689	Here we review literature on the expression and regulation of TRPC6, TRPC3 and TRPC5 in various cell types of the vertebrate kidney, the evidence that these channels are dysregulated in disease models, and research showing that knock-out or pharmacological inhibition of these channels can reduce the severity of kidney disease.
1005	30953689	TRPC6 can form a functional heteromultimer with TRPC3, and it has been suggested that TRPC5 may also play a role in glomerular disease progression, although the evidence on this is contradictory.
1006	30953689	Here we review literature on the expression and regulation of TRPC6, TRPC3 and TRPC5 in various cell types of the vertebrate kidney, the evidence that these channels are dysregulated in disease models, and research showing that knock-out or pharmacological inhibition of these channels can reduce the severity of kidney disease.
1007	31118506	Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease.
1008	31118506	MYH9, a widely expressed gene encoding nonmuscle myosin heavy chain, is also expressed in podocytes and is associated with glomerular pathophysiology.
1009	31118506	MYH9 expression was decreased in glomeruli from diabetic patients and animals and in podocytes treated with Ang II in vitro.
1010	31118506	Ang II treatment and siRNA-mediated MYH9 knockdown in podocytes resulted in actin cytoskeleton reorganization, reduced cell adhesion, actin-associated protein downregulation, and increased albumin permeability.
1011	31118506	Ang II treatment increased NOX4 expression and ROS generation.
1012	31118506	The Ang II receptor blocker losartan and the ROS scavenger NAC restored MYH9 expression in Ang II-treated podocytes, attenuated disrupted actin cytoskeleton and decreased albumin permeability.
1013	31118506	Furthermore, MYH9 overexpression in podocytes restored the effects of Ang II on the actin cytoskeleton and actin-associated proteins.
1014	31118506	Ang II-mediated TRPC6 activation reduced MYH9 expression.
1015	31118506	These results suggest that Ang II-mediated MYH9 depletion in diabetic nephropathy may increase filtration barrier permeability by inducing structural and functional podocyte injury through TRPC6-mediated Ca²⁺ influx by NOX4-mediated ROS generation.
1016	31118506	Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease.
1017	31118506	MYH9, a widely expressed gene encoding nonmuscle myosin heavy chain, is also expressed in podocytes and is associated with glomerular pathophysiology.
1018	31118506	MYH9 expression was decreased in glomeruli from diabetic patients and animals and in podocytes treated with Ang II in vitro.
1019	31118506	Ang II treatment and siRNA-mediated MYH9 knockdown in podocytes resulted in actin cytoskeleton reorganization, reduced cell adhesion, actin-associated protein downregulation, and increased albumin permeability.
1020	31118506	Ang II treatment increased NOX4 expression and ROS generation.
1021	31118506	The Ang II receptor blocker losartan and the ROS scavenger NAC restored MYH9 expression in Ang II-treated podocytes, attenuated disrupted actin cytoskeleton and decreased albumin permeability.
1022	31118506	Furthermore, MYH9 overexpression in podocytes restored the effects of Ang II on the actin cytoskeleton and actin-associated proteins.
1023	31118506	Ang II-mediated TRPC6 activation reduced MYH9 expression.
1024	31118506	These results suggest that Ang II-mediated MYH9 depletion in diabetic nephropathy may increase filtration barrier permeability by inducing structural and functional podocyte injury through TRPC6-mediated Ca²⁺ influx by NOX4-mediated ROS generation.
1025	31266804	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
1026	31266804	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
1027	31266804	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca²⁺ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
1028	31266804	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
1029	31266804	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
1030	31266804	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
1031	31266804	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca²⁺ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
1032	31266804	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
1033	31266804	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
1034	31266804	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
1035	31266804	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca²⁺ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
1036	31266804	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
1037	31266804	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
1038	31266804	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
1039	31266804	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca²⁺ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
1040	31266804	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
1041	31281825	This study is aimed at exploring the mechanism by which the -254C>G single nucleotide polymorphism (SNP) on the transient receptor potential cation channel 6 (TRPC6) gene promoter could increase its activation in steroid-resistant nephrotic syndrome children of China.
1042	31281825	We further predicted and verified that this variation was mediated by the nuclear factor kappa B (NF-κB) subunit RELA, and TNF-α significantly enhanced the transcription activity of TRPC6 with the -254G allele.
1043	31281825	This study is aimed at exploring the mechanism by which the -254C>G single nucleotide polymorphism (SNP) on the transient receptor potential cation channel 6 (TRPC6) gene promoter could increase its activation in steroid-resistant nephrotic syndrome children of China.
1044	31281825	We further predicted and verified that this variation was mediated by the nuclear factor kappa B (NF-κB) subunit RELA, and TNF-α significantly enhanced the transcription activity of TRPC6 with the -254G allele.
1045	31529341	TRPC6 and NPHS2 gene variants in adult patients with steroid-resistant nephrotic syndrome in North-West of Iran.
1046	31529341	Whole exons of NPHS2 gene and -254 C > G, -218 C > T, and -361 A > T polymorphisms in the promoter of TRPC6 gene were studied.
1047	31529341	Podocin related mutations are not too much associated with SRNS in adults, but we should consider the possibility of TRPC6 gene mutation in this population.
1048	31529341	TRPC6 and NPHS2 gene variants in adult patients with steroid-resistant nephrotic syndrome in North-West of Iran.
1049	31529341	Whole exons of NPHS2 gene and -254 C > G, -218 C > T, and -361 A > T polymorphisms in the promoter of TRPC6 gene were studied.
1050	31529341	Podocin related mutations are not too much associated with SRNS in adults, but we should consider the possibility of TRPC6 gene mutation in this population.
1051	31529341	TRPC6 and NPHS2 gene variants in adult patients with steroid-resistant nephrotic syndrome in North-West of Iran.
1052	31529341	Whole exons of NPHS2 gene and -254 C > G, -218 C > T, and -361 A > T polymorphisms in the promoter of TRPC6 gene were studied.
1053	31529341	Podocin related mutations are not too much associated with SRNS in adults, but we should consider the possibility of TRPC6 gene mutation in this population.
1054	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1055	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1056	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1057	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1058	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1059	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1060	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1061	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1062	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1063	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1064	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1065	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1066	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1067	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1068	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1069	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1070	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1071	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1072	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1073	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1074	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1075	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1076	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1077	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1078	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1079	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1080	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1081	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1082	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1083	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1084	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1085	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1086	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1087	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1088	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1089	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1090	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1091	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1092	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1093	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1094	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1095	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1096	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1097	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1098	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1099	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1100	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1101	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1102	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1103	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1104	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1105	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1106	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1107	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1108	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1109	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1110	31566428	High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.
1111	31566428	The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function.
1112	31566428	Gain of TRPC6 function and loss of podocin function induce podocyte injury.
1113	31566428	We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.
1114	31566428	Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose.
1115	31566428	High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys.
1116	31566428	The decreased podocin was diminished in TRPC6 knockdown podocytes.
1117	31566428	These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.
1118	31704171	Human genetics point to three additional TRP channels as plausible therapeutic targets: TRPC6 in FSGS, PKD2 in polycystic kidney disease, and TRPM6 in familial hypomagnesemia with secondary hypocalcemia (HSH).
1119	31784544	Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria.
1120	31784544	Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2).
1121	31784544	ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium.
1122	31784544	Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.
1123	31784544	Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria.
1124	31784544	Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2).
1125	31784544	ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium.
1126	31784544	Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.
1127	31784544	Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria.
1128	31784544	Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2).
1129	31784544	ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium.
1130	31784544	Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.
1131	31865328	Taurine Supplementation Reverses Diabetes-Induced Podocytes Injury via Modulation of the CSE/TRPC6 Axis and Improvement of Mitochondrial Function.
1132	31877991	This review highlights the data implicating TRPC6 and other TRPC family members in both genetic and non-genetic forms of kidney disease, focusing on TRPC3, TRPC5, and TRPC6 in a cell type (glomerular podocytes) that plays a key role in proteinuric kidney diseases.
1133	32123821	STZ treatment resulted in increased urine albumin excretion at 4, 8, and 10 weeks after injection, and this effect was equally severe in Trpc6 ^wt/wt and Trpc6 ^del/del rats.
1134	32123821	TRPC6 inactivation had no effect on blood urea nitrogen (BUN), plasma creatinine concentration, urine nephrin excretion, or kidney weight:body weight ratio measured 10 weeks after STZ injection.
1135	32123821	STZ treatment resulted in increased urine albumin excretion at 4, 8, and 10 weeks after injection, and this effect was equally severe in Trpc6 ^wt/wt and Trpc6 ^del/del rats.
1136	32123821	TRPC6 inactivation had no effect on blood urea nitrogen (BUN), plasma creatinine concentration, urine nephrin excretion, or kidney weight:body weight ratio measured 10 weeks after STZ injection.
1137	32617419	Several proteins including podocin, nephrin, CD2AP, and TRPC6 form a macromolecular assembly and constitute the slit-diaphragm.
1138	32617419	Podocin shares 44% homology with stomatin family proteins and similar to the stomatin proteins, podocin was shown to associate into higher-order oligomers at the site of slit-diaphragm.
1139	32779844	Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.
1140	32779844	Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well.
1141	32779844	In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation.
1142	32779844	The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects.
1143	32779844	HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid.
1144	32779844	Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions.
1145	32779844	These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
1146	32779844	Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.
1147	32779844	Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well.
1148	32779844	In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation.
1149	32779844	The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects.
1150	32779844	HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid.
1151	32779844	Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions.
1152	32779844	These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
1153	32779844	Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.
1154	32779844	Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well.
1155	32779844	In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation.
1156	32779844	The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects.
1157	32779844	HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid.
1158	32779844	Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions.
1159	32779844	These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
1160	32779844	Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.
1161	32779844	Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well.
1162	32779844	In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation.
1163	32779844	The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects.
1164	32779844	HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid.
1165	32779844	Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions.
1166	32779844	These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
1167	32779844	Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.
1168	32779844	Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well.
1169	32779844	In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation.
1170	32779844	The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects.
1171	32779844	HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid.
1172	32779844	Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions.
1173	32779844	These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
1174	32779844	Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.
1175	32779844	Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well.
1176	32779844	In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation.
1177	32779844	The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects.
1178	32779844	HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid.
1179	32779844	Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions.
1180	32779844	These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
1181	32865014	ADR-treated mice exhibited severe proteinuria, hypoalbuminemia and hyperlipidemia, glomerulosclerosis, podocyte loss, tubulointerstitial fibrosis, and oxidative stress, accompanied by elevated urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, all of which were significantly attenuated by PRO20.
1182	32865014	Urinary and renal renin activity and angiotensin II were elevated by ADR and suppressed by PRO20.
1183	32865014	In parallel, urinary and renal H₂O₂ levels and renal NADPH oxidase 4 (Nox4) and transient receptor potential channel C6 (TRPC6) expression in response to ADR were all similarly suppressed.
1184	32865014	Taken together, the results of the present study provide the first evidence that PRO20 can protect against podocyte damage and interstitial fibrosis in ADR nephropathy by preventing activation of the intrarenal renin-angiotensin system and upregulation of Nox4 and TRPC6 expression.
1185	32865014	ADR-treated mice exhibited severe proteinuria, hypoalbuminemia and hyperlipidemia, glomerulosclerosis, podocyte loss, tubulointerstitial fibrosis, and oxidative stress, accompanied by elevated urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, all of which were significantly attenuated by PRO20.
1186	32865014	Urinary and renal renin activity and angiotensin II were elevated by ADR and suppressed by PRO20.
1187	32865014	In parallel, urinary and renal H₂O₂ levels and renal NADPH oxidase 4 (Nox4) and transient receptor potential channel C6 (TRPC6) expression in response to ADR were all similarly suppressed.
1188	32865014	Taken together, the results of the present study provide the first evidence that PRO20 can protect against podocyte damage and interstitial fibrosis in ADR nephropathy by preventing activation of the intrarenal renin-angiotensin system and upregulation of Nox4 and TRPC6 expression.
1189	33015191	Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes.
1190	33015191	There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice.
1191	33015191	Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca²⁺ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2.
1192	33015191	In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.
1193	33015191	Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes.
1194	33015191	There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice.
1195	33015191	Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca²⁺ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2.
1196	33015191	In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.
1197	33015191	Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes.
1198	33015191	There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice.
1199	33015191	Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca²⁺ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2.
1200	33015191	In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.
1201	33015191	Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes.
1202	33015191	There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice.
1203	33015191	Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca²⁺ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2.
1204	33015191	In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.
1205	33891667	Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1.
1206	33891667	Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression.
1207	33891667	In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability.
1208	33922367	Therefore, we tested whether α-actinin-4 regulates the activity of TRPC6 channels.
1209	33922367	We found that co-expression of mutant α-actinin-4 K255E with TRPC6 in CHO cells decreases TRPC6 channel activity.
1210	33922367	Therefore, we tested whether α-actinin-4 regulates the activity of TRPC6 channels.
1211	33922367	We found that co-expression of mutant α-actinin-4 K255E with TRPC6 in CHO cells decreases TRPC6 channel activity.
1212	34095318	After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase.
1213	34095318	Nephrin and TRPC6 protein expression and podocyte apoptotic rates in vivo and in vitro were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively.
1214	34095318	Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2.
1215	34095318	Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes.
1216	34095318	After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase.
1217	34095318	Nephrin and TRPC6 protein expression and podocyte apoptotic rates in vivo and in vitro were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively.
1218	34095318	Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2.
1219	34095318	Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes.
1220	34288970	Nephrin, KIRREL1, podocin, CD2AP, and TRPC6 are crucial members of the SD that interact with each other and contribute to the SD's structural and functional integrity.
1221	34288970	We found a diverse distribution of nephrin and KIRREL1 ranging from nematodes to higher vertebrates, whereas podocin, CD2AP, and TRPC6 are restricted to the vertebrates.
1222	34288970	Among invertebrates, nephrin and its orthologs consist of more immunoglobulin-3 domains, whereas in the vertebrates, CD80-like C2-set domains are predominant.
1223	34288970	Nephrin, KIRREL1, podocin, CD2AP, and TRPC6 are crucial members of the SD that interact with each other and contribute to the SD's structural and functional integrity.
1224	34288970	We found a diverse distribution of nephrin and KIRREL1 ranging from nematodes to higher vertebrates, whereas podocin, CD2AP, and TRPC6 are restricted to the vertebrates.
1225	34288970	Among invertebrates, nephrin and its orthologs consist of more immunoglobulin-3 domains, whereas in the vertebrates, CD80-like C2-set domains are predominant.
1226	34371008	High glucose concentrations stimulated reactive oxygen species production through NADPH oxidase activation, decreased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and reduced deacetylase sirtuin 1 (SIRT1) protein levels and activity.
1227	34371008	Calcium signaling involving transient receptor potential cation channel C, member 6 (TRPC6) also was demonstrated to play an essential role in the regulation of insulin-dependent signaling and glucose uptake in podocytes.
1228	34680477	DUOX1 and 2 are NOX enzymes that require calcium for their activation which enters renal cells through the pivotal TRPC channels.
1229	34680477	Our results show that treatment with liraglutide, metformin or their combination ameliorates DKD by rectifying renal function tests and protecting against fibrosis paralleled by restored mRNA levels of nephrin, DUOX1 and 2, and reduced ROS production.
1230	34680477	Furthermore, TRPC6 was found to be directly interacting with nephrin, and indirectly interacting with DUOX1, DUOX2 and GLP1-R.
1231	34780752	In fructose-exposed conditionally immortalized human podocytes, we found that atractylodin inhibited podocyte hypermotility, and up-regulated slit diaphragm proteins podocin and nephrin, and cytoskeleton protein CD2-associated protein (CD2AP), α-Actinin-4 and synaptopodin expression, which were consistent with its anti-oxidative activity evidenced by up-regulation of catalase (CAT) and superoxide dismutase (SOD) 1 expression, and reduction of reactive oxygen species (ROS) production.
1232	34780752	Atractylodin also significantly suppressed expression of transient receptor potential channels 6 (TRPC6) and phosphorylated Ca²⁺/calmodulin-dependent protein kinase IV (CaMK4) in cultured podocytes with fructose exposure.
1233	34780752	Additionally, in fructose-exposed podocytes, CaMK4 siRNA up-regulated synaptopodin and reduced podocyte hypermotility, whereas, silencing of TRPC6 by siRNA decreased p-CaMK4 expression, inhibited podocyte hypermotility, showing TRPC6/p-CaMK4 signaling activation in podocyte hypermotility under fructose condition.
1234	34780752	These results first demonstrated that the anti-oxidative property of atractylodin may contribute to the suppression of podocyte hypermotility via inhibiting TRPC6/p-CaMK4 signaling and restoring synaptopodin expression abnormality.
1235	34780752	In fructose-exposed conditionally immortalized human podocytes, we found that atractylodin inhibited podocyte hypermotility, and up-regulated slit diaphragm proteins podocin and nephrin, and cytoskeleton protein CD2-associated protein (CD2AP), α-Actinin-4 and synaptopodin expression, which were consistent with its anti-oxidative activity evidenced by up-regulation of catalase (CAT) and superoxide dismutase (SOD) 1 expression, and reduction of reactive oxygen species (ROS) production.
1236	34780752	Atractylodin also significantly suppressed expression of transient receptor potential channels 6 (TRPC6) and phosphorylated Ca²⁺/calmodulin-dependent protein kinase IV (CaMK4) in cultured podocytes with fructose exposure.
1237	34780752	Additionally, in fructose-exposed podocytes, CaMK4 siRNA up-regulated synaptopodin and reduced podocyte hypermotility, whereas, silencing of TRPC6 by siRNA decreased p-CaMK4 expression, inhibited podocyte hypermotility, showing TRPC6/p-CaMK4 signaling activation in podocyte hypermotility under fructose condition.
1238	34780752	These results first demonstrated that the anti-oxidative property of atractylodin may contribute to the suppression of podocyte hypermotility via inhibiting TRPC6/p-CaMK4 signaling and restoring synaptopodin expression abnormality.
1239	34780752	In fructose-exposed conditionally immortalized human podocytes, we found that atractylodin inhibited podocyte hypermotility, and up-regulated slit diaphragm proteins podocin and nephrin, and cytoskeleton protein CD2-associated protein (CD2AP), α-Actinin-4 and synaptopodin expression, which were consistent with its anti-oxidative activity evidenced by up-regulation of catalase (CAT) and superoxide dismutase (SOD) 1 expression, and reduction of reactive oxygen species (ROS) production.
1240	34780752	Atractylodin also significantly suppressed expression of transient receptor potential channels 6 (TRPC6) and phosphorylated Ca²⁺/calmodulin-dependent protein kinase IV (CaMK4) in cultured podocytes with fructose exposure.
1241	34780752	Additionally, in fructose-exposed podocytes, CaMK4 siRNA up-regulated synaptopodin and reduced podocyte hypermotility, whereas, silencing of TRPC6 by siRNA decreased p-CaMK4 expression, inhibited podocyte hypermotility, showing TRPC6/p-CaMK4 signaling activation in podocyte hypermotility under fructose condition.
1242	34780752	These results first demonstrated that the anti-oxidative property of atractylodin may contribute to the suppression of podocyte hypermotility via inhibiting TRPC6/p-CaMK4 signaling and restoring synaptopodin expression abnormality.
1243	34978536	Here we show direct visual evidence that podocytes can sense mechanical overload (increased glomerular capillary pressure) and metabolic alterations (increased plasma glucose) via TRPC6 and purinergic receptors including P2Y2.
1244	34978536	Multiphoton microscopy of podocyte [Ca2+]i was performed in vivo using wild-type and TRPC6 or P2Y2 knockout (KO) mice expressing the calcium reporter GCaMP3/5 only in podocytes and in vitro using freshly dissected microperfused glomeruli.
1245	34978536	These responses were blocked in TRPC6 and P2Y2 KO mice.
1246	34978536	Here we show direct visual evidence that podocytes can sense mechanical overload (increased glomerular capillary pressure) and metabolic alterations (increased plasma glucose) via TRPC6 and purinergic receptors including P2Y2.
1247	34978536	Multiphoton microscopy of podocyte [Ca2+]i was performed in vivo using wild-type and TRPC6 or P2Y2 knockout (KO) mice expressing the calcium reporter GCaMP3/5 only in podocytes and in vitro using freshly dissected microperfused glomeruli.
1248	34978536	These responses were blocked in TRPC6 and P2Y2 KO mice.
1249	34978536	Here we show direct visual evidence that podocytes can sense mechanical overload (increased glomerular capillary pressure) and metabolic alterations (increased plasma glucose) via TRPC6 and purinergic receptors including P2Y2.
1250	34978536	Multiphoton microscopy of podocyte [Ca2+]i was performed in vivo using wild-type and TRPC6 or P2Y2 knockout (KO) mice expressing the calcium reporter GCaMP3/5 only in podocytes and in vitro using freshly dissected microperfused glomeruli.
1251	34978536	These responses were blocked in TRPC6 and P2Y2 KO mice.
1252	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1253	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1254	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1255	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1256	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1257	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1258	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1259	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1260	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1261	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1262	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1263	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1264	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1265	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1266	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1267	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1268	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1269	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1270	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1271	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1272	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1273	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1274	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1275	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1276	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1277	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1278	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1279	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1280	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1281	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1282	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1283	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1284	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1285	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1286	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1287	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1288	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1289	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1290	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1291	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1292	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1293	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1294	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1295	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1296	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1297	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1298	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1299	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1300	23657570	Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
1301	23657570	Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
1302	23657570	Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082).
1303	23657570	Podocin and TRPC6 interact at their respective COOH termini.
1304	23657570	Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog.
1305	23657570	These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation.
1306	23657570	They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene.
1307	23657570	Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
1308	19052171	In this study, we show by coimmunoprecipitation and GST pull-down assays that BK(Ca) channels can associate with endogenous TRPC3 and TRPC6 channels in differentiated cells of a podocyte cell line.
1309	19052171	In HEK293T cells, coexpression of TRPC6 increased surface expression of a Slo1 subunit splice variant (Slo1(VEDEC)) that is typically retained in intracellular compartments, as assessed by cell-surface biotinylation assays and confocal microscopy.
1310	19052171	In podocytes, small interfering RNA knockdown of endogenous TRPC6 reduced steady-state surface expression of endogenous Slo1 channels, but knockdown of TRPC3 had no effect.
1311	19052171	TRPC6, but not TRPC3 knockdown also reduced voltage-evoked outward current through podocyte BK(Ca) channels.
1312	19052171	These data indicate that TRPC6 and TRPC3 channels can bind to Slo1, and this colocalization may allow them to serve as a source of Ca(2+) for the activation of BK(Ca) channels.
1313	19052171	In this study, we show by coimmunoprecipitation and GST pull-down assays that BK(Ca) channels can associate with endogenous TRPC3 and TRPC6 channels in differentiated cells of a podocyte cell line.
1314	19052171	In HEK293T cells, coexpression of TRPC6 increased surface expression of a Slo1 subunit splice variant (Slo1(VEDEC)) that is typically retained in intracellular compartments, as assessed by cell-surface biotinylation assays and confocal microscopy.
1315	19052171	In podocytes, small interfering RNA knockdown of endogenous TRPC6 reduced steady-state surface expression of endogenous Slo1 channels, but knockdown of TRPC3 had no effect.
1316	19052171	TRPC6, but not TRPC3 knockdown also reduced voltage-evoked outward current through podocyte BK(Ca) channels.
1317	19052171	These data indicate that TRPC6 and TRPC3 channels can bind to Slo1, and this colocalization may allow them to serve as a source of Ca(2+) for the activation of BK(Ca) channels.
1318	19052171	In this study, we show by coimmunoprecipitation and GST pull-down assays that BK(Ca) channels can associate with endogenous TRPC3 and TRPC6 channels in differentiated cells of a podocyte cell line.
1319	19052171	In HEK293T cells, coexpression of TRPC6 increased surface expression of a Slo1 subunit splice variant (Slo1(VEDEC)) that is typically retained in intracellular compartments, as assessed by cell-surface biotinylation assays and confocal microscopy.
1320	19052171	In podocytes, small interfering RNA knockdown of endogenous TRPC6 reduced steady-state surface expression of endogenous Slo1 channels, but knockdown of TRPC3 had no effect.
1321	19052171	TRPC6, but not TRPC3 knockdown also reduced voltage-evoked outward current through podocyte BK(Ca) channels.
1322	19052171	These data indicate that TRPC6 and TRPC3 channels can bind to Slo1, and this colocalization may allow them to serve as a source of Ca(2+) for the activation of BK(Ca) channels.
1323	19052171	In this study, we show by coimmunoprecipitation and GST pull-down assays that BK(Ca) channels can associate with endogenous TRPC3 and TRPC6 channels in differentiated cells of a podocyte cell line.
1324	19052171	In HEK293T cells, coexpression of TRPC6 increased surface expression of a Slo1 subunit splice variant (Slo1(VEDEC)) that is typically retained in intracellular compartments, as assessed by cell-surface biotinylation assays and confocal microscopy.
1325	19052171	In podocytes, small interfering RNA knockdown of endogenous TRPC6 reduced steady-state surface expression of endogenous Slo1 channels, but knockdown of TRPC3 had no effect.
1326	19052171	TRPC6, but not TRPC3 knockdown also reduced voltage-evoked outward current through podocyte BK(Ca) channels.
1327	19052171	These data indicate that TRPC6 and TRPC3 channels can bind to Slo1, and this colocalization may allow them to serve as a source of Ca(2+) for the activation of BK(Ca) channels.
1328	19052171	In this study, we show by coimmunoprecipitation and GST pull-down assays that BK(Ca) channels can associate with endogenous TRPC3 and TRPC6 channels in differentiated cells of a podocyte cell line.
1329	19052171	In HEK293T cells, coexpression of TRPC6 increased surface expression of a Slo1 subunit splice variant (Slo1(VEDEC)) that is typically retained in intracellular compartments, as assessed by cell-surface biotinylation assays and confocal microscopy.
1330	19052171	In podocytes, small interfering RNA knockdown of endogenous TRPC6 reduced steady-state surface expression of endogenous Slo1 channels, but knockdown of TRPC3 had no effect.
1331	19052171	TRPC6, but not TRPC3 knockdown also reduced voltage-evoked outward current through podocyte BK(Ca) channels.
1332	19052171	These data indicate that TRPC6 and TRPC3 channels can bind to Slo1, and this colocalization may allow them to serve as a source of Ca(2+) for the activation of BK(Ca) channels.
1333	22828802	This effect of NMDA was associated with increased cell-surface expression of p47(phox), a cytosolic regulatory subunit of the NADPH oxidase NOX2.
1334	22828802	NMDA treatment also evoked robust activation of Rho but not Rac,consistent with previous studies of downstream effectors of TRPC6 activation.
1335	22828802	Exposing cells to NMDA for 24 h reduced total and cell surface expression of the podocyte markers nephrin and podocin, but there was no loss of cells.
1336	22828802	With longer NMDA exposure (72 h), we observed loss of cells associated with nuclear fragmentation and increased expression of caspase-3, caspase-6, and Bax, suggesting an apoptotic process.
1337	24850910	Angiotensin II and canonical transient receptor potential-6 activation stimulate release of a signal transducer and activator of transcription 3-activating factor from mouse podocytes.
1338	24850910	Here, we have observed that application of 100 nM angiotensin II (Ang II) to cultured podocytes for 6-24 hours causes a marked increase in the phosphorylation of STAT3 on tyrosine Y705 but has no effect on phosphorylation at serine S727.
1339	24850910	By contrast, Ang II treatment of short periods (20-60 minutes) caused a small but consistent suppression of tyrosine phosphylation of STAT3.
1340	24850910	The stimulatory effects of Ang II on STAT3 phosphorylation were abolished by small-interfering RNA knockdown of TRPC6 and also by inhibitors of the Ca(2+)-dependent downstream enzymes calcineurin and Ca(2+)-calmodulin-dependent protein kinase II.
1341	24850910	By contrast, the inhibitory effect of Ang II on STAT3 phosphorylation persists with frequent medium changes.
1342	24850910	Experiments with neutralizing and inhibitory antibodies suggest that the STAT3 stimulatory factor secreted from podocytes is not interleukin-6, but also suggest that this factor exerts its actions through a receptor system that requires glycoprotein 130.