Ignet

Gene Information

Gene symbol: CRTC1

Gene name: CREB regulated transcription coactivator 1

HGNC ID: 16062

Synonyms: KIAA0616, FLJ14027, TORC1

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	ACOX1	1 hits
3	ACTC1	1 hits
4	AKT1	1 hits
5	ALB	1 hits
6	CCL2	1 hits
7	CFB	1 hits
8	COL1A1	1 hits
9	CPT1A	1 hits
10	CRTC2	1 hits
11	EIF4EBP1	1 hits
12	FASN	1 hits
13	HK2	1 hits
14	JUN	1 hits
15	KPNA2	1 hits
16	MAPK3	1 hits
17	MIRN214	1 hits
18	MLXIPL	1 hits
19	NOX4	1 hits
20	NPHS1	1 hits
21	NPHS2	1 hits
22	PDK1	1 hits
23	PIK3CA	1 hits
24	PPP2R4	1 hits
25	PRKAA2	1 hits
26	PRKCA	1 hits
27	PTEN	1 hits
28	RORC	1 hits
29	RPS6KB1	1 hits
30	SERPINE1	1 hits
31	SIRT1	1 hits
32	SLC1A5	1 hits
33	SLC43A1	1 hits
34	STAT1	1 hits
35	TENC1	1 hits
36	TRPC6	1 hits
37	TXNIP	1 hits
38	VIM	1 hits

Related Sentences

#	PMID	Sentence
1	20498248	Mammalian target of rapamycin (mTOR) is the core component of two complexes, mTORC1 and mTORC2. mTORC1 is inhibited by rapamycin and analogues. mTORC2 is impeded only in some cell types by prolonged exposure to these compounds. mTOR activation is linked to tubular cell proliferation in animal models and human autosomal dominant polycystic kidney disease (ADPKD). mTOR inhibitors impede cell proliferation and cyst growth in polycystic kidney disease (PKD) models.
2	21606591	Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis.
3	21606591	Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis.
4	21606591	Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis.
5	21606591	Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis.
6	22773827	We generated transgenic Fischer 344 rats that express a dominant negative AA-4E-BP1 transgene driven by the podocin promoter; a member of the mammalian target of rapamycin complex 1 (mTORC1) pathway, 4E-BP1 modulates cap-dependent translation, which is a key determinant of a cell's hypertrophic response to nutrients and growth factors.
7	23268354	The SLC43 family is composed of only three genes coding for the plasma membrane facilitator system l amino acid transporters LAT3 (SLC43A1; TC 2.A.1.44.1) and LAT4 (SLC43A2; TC 2.A.1.44.2), and the orphan protein EEG1 (SLC43A3; TC 2.A.1.44.3).
8	23268354	Besides the known mechanism of transport of LAT3 and LAT4, their physiological roles still remain quite obscure.
9	23268354	Finally, LAT3 is up-regulated in androgen-dependent cancers, suggesting a role in mTORC1 signaling in this type of tumors.
10	23268354	Unfortunately, the EEG1 mouse model (EEG1(Y221∗)) described here has not yet offered a clue to the physiological role of this orphan protein.
11	24493874	Both mTOR complexes, mTORC1 and mTORC2, regulate such diverse processes as glomerular filtration and the fine tuning of tubular electrolyte balance.
12	25126552	Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney.
13	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.
14	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.
15	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
16	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
17	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.
18	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.
19	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.
20	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
21	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
22	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.
23	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.
24	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.
25	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
26	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
27	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.
28	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.
29	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.
30	25393730	The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2.
31	25393730	In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed.
32	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.
33	25724269	Independent role of PP2A and mTORc1 in palmitate induced podocyte death.
34	25724269	This impairment in insulin signalling prevents insulin induced SIRT 1 expression and deacetylation of p53.
35	25724269	Further, palmitate treatment prevents insulin induced phosphorylation of PP2A and FOXO1 but it potentiates the phosphorylation of mTOR at Ser 2448.
36	25724269	Interestingly, selective inhibition of PP2A, by Okadaic acid at 5 nM, restored insulin induced phosphorylation of AKT, FOXO1, SIRT1 activity and p53 degradation.
37	25724269	On the other hand, partial inhibition of mTORc1, by low dose of Rapamycin (1 nM) also restored phosphorylation of AKT and SIRT1 activity, whereas no significant changes were observed in insulin induced phosphorylation of PP2A after mTORc1 inhibition.
38	25724269	To the best of our knowledge this is the first report suggesting independent role of PP2A and mTORc1 in palmitate induced IR and associated podocyte death.
39	25724269	Therefore, the best therapeutic approach for treatment of diabetic kidney disease should involve manipulating phosphorylation of both PP2A and mTORc1.
40	25724269	Independent role of PP2A and mTORc1 in palmitate induced podocyte death.
41	25724269	This impairment in insulin signalling prevents insulin induced SIRT 1 expression and deacetylation of p53.
42	25724269	Further, palmitate treatment prevents insulin induced phosphorylation of PP2A and FOXO1 but it potentiates the phosphorylation of mTOR at Ser 2448.
43	25724269	Interestingly, selective inhibition of PP2A, by Okadaic acid at 5 nM, restored insulin induced phosphorylation of AKT, FOXO1, SIRT1 activity and p53 degradation.
44	25724269	On the other hand, partial inhibition of mTORc1, by low dose of Rapamycin (1 nM) also restored phosphorylation of AKT and SIRT1 activity, whereas no significant changes were observed in insulin induced phosphorylation of PP2A after mTORc1 inhibition.
45	25724269	To the best of our knowledge this is the first report suggesting independent role of PP2A and mTORc1 in palmitate induced IR and associated podocyte death.
46	25724269	Therefore, the best therapeutic approach for treatment of diabetic kidney disease should involve manipulating phosphorylation of both PP2A and mTORc1.
47	25724269	Independent role of PP2A and mTORc1 in palmitate induced podocyte death.
48	25724269	This impairment in insulin signalling prevents insulin induced SIRT 1 expression and deacetylation of p53.
49	25724269	Further, palmitate treatment prevents insulin induced phosphorylation of PP2A and FOXO1 but it potentiates the phosphorylation of mTOR at Ser 2448.
50	25724269	Interestingly, selective inhibition of PP2A, by Okadaic acid at 5 nM, restored insulin induced phosphorylation of AKT, FOXO1, SIRT1 activity and p53 degradation.
51	25724269	On the other hand, partial inhibition of mTORc1, by low dose of Rapamycin (1 nM) also restored phosphorylation of AKT and SIRT1 activity, whereas no significant changes were observed in insulin induced phosphorylation of PP2A after mTORc1 inhibition.
52	25724269	To the best of our knowledge this is the first report suggesting independent role of PP2A and mTORc1 in palmitate induced IR and associated podocyte death.
53	25724269	Therefore, the best therapeutic approach for treatment of diabetic kidney disease should involve manipulating phosphorylation of both PP2A and mTORc1.
54	26565025	Transforming Growth Factor β1-induced Apoptosis in Podocytes via the Extracellular Signal-regulated Kinase-Mammalian Target of Rapamycin Complex 1-NADPH Oxidase 4 Axis.
55	26565025	Here we investigated the regulatory mechanism of Nox4 up-regulation by mTORC1 activation on TGF-β1-induced apoptosis in immortalized podocytes.
56	26565025	Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-β1.
57	26565025	Inhibition of either ERK1/2 or mTORC1 did not reduce the TGF-β1-stimulated increase in Nox4 mRNA level but significantly inhibited total Nox4 expression, ROS generation, and apoptosis induced by TGF-β1.
58	26565025	Moreover, double knockdown of Smad2 and 3 or only Smad4 completely suppressed TGF-β1-induced ERK1/2-mTORactivation.
59	26565025	Transforming Growth Factor β1-induced Apoptosis in Podocytes via the Extracellular Signal-regulated Kinase-Mammalian Target of Rapamycin Complex 1-NADPH Oxidase 4 Axis.
60	26565025	Here we investigated the regulatory mechanism of Nox4 up-regulation by mTORC1 activation on TGF-β1-induced apoptosis in immortalized podocytes.
61	26565025	Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-β1.
62	26565025	Inhibition of either ERK1/2 or mTORC1 did not reduce the TGF-β1-stimulated increase in Nox4 mRNA level but significantly inhibited total Nox4 expression, ROS generation, and apoptosis induced by TGF-β1.
63	26565025	Moreover, double knockdown of Smad2 and 3 or only Smad4 completely suppressed TGF-β1-induced ERK1/2-mTORactivation.
64	26565025	Transforming Growth Factor β1-induced Apoptosis in Podocytes via the Extracellular Signal-regulated Kinase-Mammalian Target of Rapamycin Complex 1-NADPH Oxidase 4 Axis.
65	26565025	Here we investigated the regulatory mechanism of Nox4 up-regulation by mTORC1 activation on TGF-β1-induced apoptosis in immortalized podocytes.
66	26565025	Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-β1.
67	26565025	Inhibition of either ERK1/2 or mTORC1 did not reduce the TGF-β1-stimulated increase in Nox4 mRNA level but significantly inhibited total Nox4 expression, ROS generation, and apoptosis induced by TGF-β1.
68	26565025	Moreover, double knockdown of Smad2 and 3 or only Smad4 completely suppressed TGF-β1-induced ERK1/2-mTORactivation.
69	26790279	Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K).
70	27477490	Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport.
71	27477490	Novel insights into the roles of mTORC1 and mTORC2 in the regulation of immune cell homeostasis and function are helping to improve understanding of the complex effects of mTOR targeting on immune responses, including those that impact both de novo renal disease and renal allograft outcomes.
72	27477490	As understanding of the mechanisms by which mTORC1 and mTORC2 drive the pathogenesis of renal disease progresses, clinical studies of mTOR pathway targeting will enable testing of evolving hypotheses.
73	27477490	Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport.
74	27477490	Novel insights into the roles of mTORC1 and mTORC2 in the regulation of immune cell homeostasis and function are helping to improve understanding of the complex effects of mTOR targeting on immune responses, including those that impact both de novo renal disease and renal allograft outcomes.
75	27477490	As understanding of the mechanisms by which mTORC1 and mTORC2 drive the pathogenesis of renal disease progresses, clinical studies of mTOR pathway targeting will enable testing of evolving hypotheses.
76	27477490	Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport.
77	27477490	Novel insights into the roles of mTORC1 and mTORC2 in the regulation of immune cell homeostasis and function are helping to improve understanding of the complex effects of mTOR targeting on immune responses, including those that impact both de novo renal disease and renal allograft outcomes.
78	27477490	As understanding of the mechanisms by which mTORC1 and mTORC2 drive the pathogenesis of renal disease progresses, clinical studies of mTOR pathway targeting will enable testing of evolving hypotheses.
79	28955049	C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.
80	28955049	C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1.
81	28955049	Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo.
82	28955049	These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity.
83	28955049	C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.
84	28955049	C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1.
85	28955049	Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo.
86	28955049	These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity.
87	28955049	C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.
88	28955049	C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1.
89	28955049	Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo.
90	28955049	These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity.
91	28955049	C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.
92	28955049	C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1.
93	28955049	Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo.
94	28955049	These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity.
95	30444896	Both mTORC1 and mTORC2 are hyperactive in response to TGFβ in various renal diseases.
96	30444896	Pharmacological inhibitor of PI 3 kinase, Ly 294002 and pan Akt kinase inhibitor MK 2206 prevented the TGFβ induced downregulation of deptor, resulting in suppression of both mTORC1 and mTORC2 activities.
97	30444896	Inhibition of Akt2 using a phospho-deficient mutant that inactivates its kinase activity, as well as siRNA against the kinase markedly diminished TGFβ -mediated deptor suppression, its association with mTOR and activation of mTORC1 and mTORC2.
98	30444896	Thus, our data identify previously unrecognized Akt2 kinase as a driver of TGFβ induced deptor downregulation and sustained mTORC1 and mTORC2 activation.
99	30444896	Both mTORC1 and mTORC2 are hyperactive in response to TGFβ in various renal diseases.
100	30444896	Pharmacological inhibitor of PI 3 kinase, Ly 294002 and pan Akt kinase inhibitor MK 2206 prevented the TGFβ induced downregulation of deptor, resulting in suppression of both mTORC1 and mTORC2 activities.
101	30444896	Inhibition of Akt2 using a phospho-deficient mutant that inactivates its kinase activity, as well as siRNA against the kinase markedly diminished TGFβ -mediated deptor suppression, its association with mTOR and activation of mTORC1 and mTORC2.
102	30444896	Thus, our data identify previously unrecognized Akt2 kinase as a driver of TGFβ induced deptor downregulation and sustained mTORC1 and mTORC2 activation.
103	30444896	Both mTORC1 and mTORC2 are hyperactive in response to TGFβ in various renal diseases.
104	30444896	Pharmacological inhibitor of PI 3 kinase, Ly 294002 and pan Akt kinase inhibitor MK 2206 prevented the TGFβ induced downregulation of deptor, resulting in suppression of both mTORC1 and mTORC2 activities.
105	30444896	Inhibition of Akt2 using a phospho-deficient mutant that inactivates its kinase activity, as well as siRNA against the kinase markedly diminished TGFβ -mediated deptor suppression, its association with mTOR and activation of mTORC1 and mTORC2.
106	30444896	Thus, our data identify previously unrecognized Akt2 kinase as a driver of TGFβ induced deptor downregulation and sustained mTORC1 and mTORC2 activation.
107	30444896	Both mTORC1 and mTORC2 are hyperactive in response to TGFβ in various renal diseases.
108	30444896	Pharmacological inhibitor of PI 3 kinase, Ly 294002 and pan Akt kinase inhibitor MK 2206 prevented the TGFβ induced downregulation of deptor, resulting in suppression of both mTORC1 and mTORC2 activities.
109	30444896	Inhibition of Akt2 using a phospho-deficient mutant that inactivates its kinase activity, as well as siRNA against the kinase markedly diminished TGFβ -mediated deptor suppression, its association with mTOR and activation of mTORC1 and mTORC2.
110	30444896	Thus, our data identify previously unrecognized Akt2 kinase as a driver of TGFβ induced deptor downregulation and sustained mTORC1 and mTORC2 activation.
111	30873046	However, the dual inhibitor of mTORC1 and mTORC2 AZD8055 and short hairpin RNA targeting Rictor downregulated BK channel mRNA and protein levels and bioactivity.
112	30873046	In addition, MK2206, GF109203X, and GSK650394, which are inhibitors of Akt, PKCα, and SGK1, respectively, were employed to test the downstream signaling pathway of mTORC2.
113	30873046	These results indicate mTORC2 not only regulates the distribution of BK channels through Akt, but also modulates BK channel protein expression via SGK1 in podocytes.
114	30906437	HG effects on podocytes were suppressed by mTOR complex 1 (mTORC1) inhibitor, rapamycin, and further suppressed by dual mTORC1 and mTORC2 inhibitor, KU0063794, when compared with podocytes that received mannitol treatment.
115	30906437	In addition, the present findings suggest that the mTORC1 and mTORC2 signaling pathways may be responsible for the cell viability and apoptosis, and that the mTORC2 pathway could be primarily responsible for the regulation of cytoskeleton-associated proteins.
116	30906437	HG effects on podocytes were suppressed by mTOR complex 1 (mTORC1) inhibitor, rapamycin, and further suppressed by dual mTORC1 and mTORC2 inhibitor, KU0063794, when compared with podocytes that received mannitol treatment.
117	30906437	In addition, the present findings suggest that the mTORC1 and mTORC2 signaling pathways may be responsible for the cell viability and apoptosis, and that the mTORC2 pathway could be primarily responsible for the regulation of cytoskeleton-associated proteins.
118	31377057	Inhibition of the ERK1/2-mTORC1 axis ameliorates proteinuria and the fibrogenic action of transforming growth factor-β in Adriamycin-induced glomerulosclerosis.
119	31377057	Here, we identified the regulation of mammalian target of rapamycin complex1 (mTORC1) by TGF-β via ERK1/2 in the Adriamycin-induced murine model of focal segmental glomerulosclerosis.
120	31377057	Phosphorylation of the TGF-β receptor-I (TGF-βRI), Smad3, ERK1/2 and ribosomal protein S6 were evident in the glomeruli of adriamycin-treated mice.
121	31377057	Targeting TGFβ-RI and mTORC1 with pharmacological inhibitors suppressed TGF-β signaling in glomeruli and significantly reduced albuminuria, glomerulosclerosis, protein levels of collagen 4α3, plasminogen activator inhibitor-1, and vimentin and restored mRNA levels of podocyte markers.
122	31377057	Low dose US Food and Drug Administration (FDA)-approved MEK/ERK inhibitor trametinib/GSK1120212 blunted TGF-β1-induced mTORC1 activation in podocytes, ameliorated up-regulation of TGF-β, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, fibronectin and α-smooth muscle actin and prevented albuminuria and glomerulosclerosis with improved serum albumin.
123	31377057	In cultured podocytes, this pathway was found to be associated with translation of fibrogenic collagen 4α3 and plasminogen activator inhibitor-1, without influencing their transcription.
124	31377057	Inhibition of the ERK1/2-mTORC1 axis ameliorates proteinuria and the fibrogenic action of transforming growth factor-β in Adriamycin-induced glomerulosclerosis.
125	31377057	Here, we identified the regulation of mammalian target of rapamycin complex1 (mTORC1) by TGF-β via ERK1/2 in the Adriamycin-induced murine model of focal segmental glomerulosclerosis.
126	31377057	Phosphorylation of the TGF-β receptor-I (TGF-βRI), Smad3, ERK1/2 and ribosomal protein S6 were evident in the glomeruli of adriamycin-treated mice.
127	31377057	Targeting TGFβ-RI and mTORC1 with pharmacological inhibitors suppressed TGF-β signaling in glomeruli and significantly reduced albuminuria, glomerulosclerosis, protein levels of collagen 4α3, plasminogen activator inhibitor-1, and vimentin and restored mRNA levels of podocyte markers.
128	31377057	Low dose US Food and Drug Administration (FDA)-approved MEK/ERK inhibitor trametinib/GSK1120212 blunted TGF-β1-induced mTORC1 activation in podocytes, ameliorated up-regulation of TGF-β, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, fibronectin and α-smooth muscle actin and prevented albuminuria and glomerulosclerosis with improved serum albumin.
129	31377057	In cultured podocytes, this pathway was found to be associated with translation of fibrogenic collagen 4α3 and plasminogen activator inhibitor-1, without influencing their transcription.
130	31377057	Inhibition of the ERK1/2-mTORC1 axis ameliorates proteinuria and the fibrogenic action of transforming growth factor-β in Adriamycin-induced glomerulosclerosis.
131	31377057	Here, we identified the regulation of mammalian target of rapamycin complex1 (mTORC1) by TGF-β via ERK1/2 in the Adriamycin-induced murine model of focal segmental glomerulosclerosis.
132	31377057	Phosphorylation of the TGF-β receptor-I (TGF-βRI), Smad3, ERK1/2 and ribosomal protein S6 were evident in the glomeruli of adriamycin-treated mice.
133	31377057	Targeting TGFβ-RI and mTORC1 with pharmacological inhibitors suppressed TGF-β signaling in glomeruli and significantly reduced albuminuria, glomerulosclerosis, protein levels of collagen 4α3, plasminogen activator inhibitor-1, and vimentin and restored mRNA levels of podocyte markers.
134	31377057	Low dose US Food and Drug Administration (FDA)-approved MEK/ERK inhibitor trametinib/GSK1120212 blunted TGF-β1-induced mTORC1 activation in podocytes, ameliorated up-regulation of TGF-β, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, fibronectin and α-smooth muscle actin and prevented albuminuria and glomerulosclerosis with improved serum albumin.
135	31377057	In cultured podocytes, this pathway was found to be associated with translation of fibrogenic collagen 4α3 and plasminogen activator inhibitor-1, without influencing their transcription.
136	31727365	In addition, silencing of KPNA2 deactivated mTORC1/p70S6K pathway activation via regulating SLC1A5.
137	31727365	Therefore, our study suggested that knockdown of KPNA2 rescued HG-induced injury via blocking activation of mTORC1/p70S6K pathway by mediating SLC1A5.
138	32051833	Renal expression of Nox4, miRNA-214, PTEN, PDK1, phosphorylated Akt, mTOR, and mTORC1 was detected.
139	32051833	Decreased expression of PTEN, as well as increased expression of Nox4, miRNA-214, PDK1, phosphorylated Akt, mTOR, and mTORC1, was detected.
140	32051833	Renal expression of Nox4, miRNA-214, PTEN, PDK1, phosphorylated Akt, mTOR, and mTORC1 was detected.
141	32051833	Decreased expression of PTEN, as well as increased expression of Nox4, miRNA-214, PDK1, phosphorylated Akt, mTOR, and mTORC1, was detected.
142	32583421	In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and thioredoxin-interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys.
143	32583421	Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme A oxidase 1 (ACOX1) in diabetic kidneys.
144	32583421	In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose (HG) conditions.
145	32583421	Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells.
146	32583421	These results indicate that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.
147	32583421	In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and thioredoxin-interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys.
148	32583421	Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme A oxidase 1 (ACOX1) in diabetic kidneys.
149	32583421	In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose (HG) conditions.
150	32583421	Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells.
151	32583421	These results indicate that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.
152	32583421	In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and thioredoxin-interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys.
153	32583421	Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme A oxidase 1 (ACOX1) in diabetic kidneys.
154	32583421	In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose (HG) conditions.
155	32583421	Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells.
156	32583421	These results indicate that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.
157	32583421	In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and thioredoxin-interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys.
158	32583421	Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme A oxidase 1 (ACOX1) in diabetic kidneys.
159	32583421	In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose (HG) conditions.
160	32583421	Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells.
161	32583421	These results indicate that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.
162	33303821	Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1.
163	33303821	Our results demonstrate that saturated FFA activated the serine/threonine kinases IκB kinase (IKK)β/IκBα and mTORC1/S6K1, but not protein kinase C and c-jun N-terminal kinase, in podocytes and glomeruli of db/db mice.
164	33303821	Using IKK, mTORC1 and ceramide production inhibitors, we were able to blunt IRS1 serine 307 phosphorylation and restore insulin stimulation of Akt.
165	34622800	Here, analyzing Gene Expression Omnibus GSE30528 data, we identified genes enriched in mTORC1 signaling, CFB, and complement alternative pathways in podocytes from patients with DKD.
166	34622800	In mouse models, podocyte mTOR complex 1 (mTORC1) signaling activation was induced, while blockade of mTORC1 signaling reduced CFB upregulation, alternative complement pathway activation, and podocyte injury in the glomeruli.
167	34622800	In cultured podocytes, high glucose treatment activated mTORC1 signaling, stimulated STAT1 phosphorylation, and upregulated CFB expression, while blockade of mTORC1 or STAT1 signaling abolished high glucose-upregulated CFB expression.
168	34622800	Additionally, high glucose levels downregulated protein phosphatase 2Acα (PP2Acα) expression, while PP2Acα deficiency enhanced high glucose-induced mTORC1/STAT1 activation, CFB induction, and podocyte injury.
169	34622800	Here, analyzing Gene Expression Omnibus GSE30528 data, we identified genes enriched in mTORC1 signaling, CFB, and complement alternative pathways in podocytes from patients with DKD.
170	34622800	In mouse models, podocyte mTOR complex 1 (mTORC1) signaling activation was induced, while blockade of mTORC1 signaling reduced CFB upregulation, alternative complement pathway activation, and podocyte injury in the glomeruli.
171	34622800	In cultured podocytes, high glucose treatment activated mTORC1 signaling, stimulated STAT1 phosphorylation, and upregulated CFB expression, while blockade of mTORC1 or STAT1 signaling abolished high glucose-upregulated CFB expression.
172	34622800	Additionally, high glucose levels downregulated protein phosphatase 2Acα (PP2Acα) expression, while PP2Acα deficiency enhanced high glucose-induced mTORC1/STAT1 activation, CFB induction, and podocyte injury.
173	34622800	Here, analyzing Gene Expression Omnibus GSE30528 data, we identified genes enriched in mTORC1 signaling, CFB, and complement alternative pathways in podocytes from patients with DKD.
174	34622800	In mouse models, podocyte mTOR complex 1 (mTORC1) signaling activation was induced, while blockade of mTORC1 signaling reduced CFB upregulation, alternative complement pathway activation, and podocyte injury in the glomeruli.
175	34622800	In cultured podocytes, high glucose treatment activated mTORC1 signaling, stimulated STAT1 phosphorylation, and upregulated CFB expression, while blockade of mTORC1 or STAT1 signaling abolished high glucose-upregulated CFB expression.
176	34622800	Additionally, high glucose levels downregulated protein phosphatase 2Acα (PP2Acα) expression, while PP2Acα deficiency enhanced high glucose-induced mTORC1/STAT1 activation, CFB induction, and podocyte injury.
177	34622800	Here, analyzing Gene Expression Omnibus GSE30528 data, we identified genes enriched in mTORC1 signaling, CFB, and complement alternative pathways in podocytes from patients with DKD.
178	34622800	In mouse models, podocyte mTOR complex 1 (mTORC1) signaling activation was induced, while blockade of mTORC1 signaling reduced CFB upregulation, alternative complement pathway activation, and podocyte injury in the glomeruli.
179	34622800	In cultured podocytes, high glucose treatment activated mTORC1 signaling, stimulated STAT1 phosphorylation, and upregulated CFB expression, while blockade of mTORC1 or STAT1 signaling abolished high glucose-upregulated CFB expression.
180	34622800	Additionally, high glucose levels downregulated protein phosphatase 2Acα (PP2Acα) expression, while PP2Acα deficiency enhanced high glucose-induced mTORC1/STAT1 activation, CFB induction, and podocyte injury.