Ignet

Gene Information

Gene symbol: ATP6AP2

Gene name: ATPase, H+ transporting, lysosomal accessory protein 2

HGNC ID: 18305

Synonyms: M8-9, APT6M8-9, ATP6M8-9

Related Genes

#	Gene Symbol	Number of hits
1	ACE	1 hits
2	AGT	1 hits
3	AGTR1	1 hits
4	ANG	1 hits
5	CCRK	1 hits
6	COX8A	1 hits
7	FOS	1 hits
8	GGT1	1 hits
9	IFI44	1 hits
10	INS	1 hits
11	MAPK1	1 hits
12	MAPK3	1 hits
13	MAPK6	1 hits
14	NOX5	1 hits
15	NR1I2	1 hits
16	NR3C2	1 hits
17	PLAT	1 hits
18	PTGS2	1 hits
19	PVRL1	1 hits
20	REN	1 hits
21	SERPINE1	1 hits

Related Sentences

#	PMID	Sentence
1	16900219	Activation of the (pro)renin receptor has profibrotic effects, and now Kaneshiroet al. show that it also increases COX-2 synthesis.
2	16940215	Tissue accumulation of circulating prorenin results in angiotensin generation, but could also, through binding to the recently cloned (pro)renin receptor, lead to angiotensin-independent effects, like p42/p44 mitogen-activated protein kinase (MAPK) activation and plasminogen-activator inhibitor (PAI)-1 release.
3	16940215	Prorenin affected neither p42/p44 MAPK nor PAI-1.
4	16940215	PAI-1 release did occur during coincubation with angiotensinogen, suggesting that this effect is angiotensin mediated.
5	16940215	Rat microarray gene (n=4800) transcription profiling of myocytes stimulated with prorenin detected 260 regulated genes (P<0.001 versus control), among which genes downstream of p38 MAPK and HSP27 involved in actin filament dynamics and (cis-)regulated genes confined in blood pressure and diabetes QTL regions, like Syntaxin-7, were overrepresented.
6	16940215	Quantitative real-time RT-PCR of 7 selected genes (Opg, Timp1, Best5, Hsp27, pro-Anp, Col3a1, and Hk2) revealed temporal regulation, with peak levels occurring after 4 hours of prorenin exposure.
7	16940215	This regulation was not altered in the presence of the renin inhibitor aliskiren or the angiotensin II type 1 receptor antagonist eprosartan.
8	16940215	Prorenin-induced stimulation of the p38 MAPK/HSP27 pathway, resulting in alterations in actin filament dynamics, may underlie the severe cardiac hypertrophy that has been described previously in rats with hepatic prorenin overexpression.
9	16959581	Recent studies have increased our understanding of the complexity of the RAAS with identification of new components of this cascade including angiotensin-converting enzyme 2 and a putative renin receptor.
10	17538189	Seventeen-week-old heminephrectomized streptozotocin-induced diabetic rats with an increased urinary protein excretion and a significant glomerulosclerosis had been treated for 12 wk with the (pro)renin receptor blocker (PRRB), angiotensin-converting enzyme inhibitor (ACEi), or vehicle peptide by using subcutaneously implanted osmotic minipumps.
11	18192338	Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity.
12	18192338	Recent studies have demonstrated the presence of the (pro)renin receptor (PRR) in the glomerular mesangium and the subendothelial layer of the renal arteries.
13	18192338	We hypothesized that diabetes upregulates PRR expression through enhanced angiotensin subtype 1 (AT1) receptor-NADPH oxidase cascade activity.
14	18192338	Using real-time polymerase chain reaction, Western blot analysis and immunostaining, we studied renal localization of the PRR in the streptozotocin-induced diabetic rat model and in response to 1 week of treatment with the AT1 receptor blocker valsartan (10 mg kg(-1) day(-1)), the angiotensin AT2 receptor blocker PD123319 (0.5 mg kg(-1) day(-1)) or the NADPH oxidase inhibitor diphenylene iodonium (DPI; 0.5 mg kg(-1) day(-1)) 6 weeks post-induction of diabetes.
15	18192338	The AT2 blocker PD123319 did not have significant effects on PRR mRNA (157%) or protein expression (200%) in the kidneys of diabetic rats.
16	18192338	Expression of the PRR is upregulated in diabetes via enhancement of AT1 receptor-NADPH oxidase activity.
17	18192338	Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity.
18	18192338	Recent studies have demonstrated the presence of the (pro)renin receptor (PRR) in the glomerular mesangium and the subendothelial layer of the renal arteries.
19	18192338	We hypothesized that diabetes upregulates PRR expression through enhanced angiotensin subtype 1 (AT1) receptor-NADPH oxidase cascade activity.
20	18192338	Using real-time polymerase chain reaction, Western blot analysis and immunostaining, we studied renal localization of the PRR in the streptozotocin-induced diabetic rat model and in response to 1 week of treatment with the AT1 receptor blocker valsartan (10 mg kg(-1) day(-1)), the angiotensin AT2 receptor blocker PD123319 (0.5 mg kg(-1) day(-1)) or the NADPH oxidase inhibitor diphenylene iodonium (DPI; 0.5 mg kg(-1) day(-1)) 6 weeks post-induction of diabetes.
21	18192338	The AT2 blocker PD123319 did not have significant effects on PRR mRNA (157%) or protein expression (200%) in the kidneys of diabetic rats.
22	18192338	Expression of the PRR is upregulated in diabetes via enhancement of AT1 receptor-NADPH oxidase activity.
23	18335185	(Pro)renin receptor-bound prorenin not only causes the generation of angiotensin II via the nonproteolytic activation of prorenin, it also activates the receptor's own intracellular signaling pathways independent of the generated angiotensin II.
24	18454253	The renin angiotensin system (RAS) and its effector molecule angiotensin II, in particular, have a range of hemodynamic and nonhemodynamic effects that contribute not only to the development of hypertension, but also to renal disease.
25	18454253	As a result, therapeutic inhibition of the RAS with angiotensin-converting enzyme inhibitors and/or selective angiotensin II type 1 receptor blockers has been proposed as a key strategy for reducing kidney damage beyond the expected effects one would observe with blood pressure reduction per se.
26	18454253	Thus, further understanding of these new components of the renin angiotensin aldosterone system (RAAS), such as the angiotensin type 2 receptor subtype, angiotensin converting enzyme 2, and the recently cloned renin receptor, is likely to have therapeutic implications for disorders such as diabetic nephropathy, where interruption of the RAAS is widely used.
27	18490518	In diabetic TG(mRen-2)27 rats, aliskiren (10 or 30 mg/kg per day, 10 weeks) lowered blood pressure, prevented albuminuria, and suppressed renal transforming growth factor-beta and collagen I expression versus vehicle.
28	18490518	In human mesangial cells, aliskiren (0.1 micromol/L to 10 micromol/L) did not inhibit binding of (125)I-renin to the (pro)renin receptor, nor did it alter the activation of extracellular signal-regulated kinase 1/2 by renin (20 nmol/L) preincubated with aliskiren (100 nmol/L) or affect gene expression of the (pro)renin receptor.
29	18490518	The evidence that aliskiren can reduce in vivo gene expression for the (pro)renin receptor and that it may block prorenin-induced angiotensin generation supports the need for additional work to reveal the mechanism of the observed renoprotection by this renin inhibitor.
30	18490518	In diabetic TG(mRen-2)27 rats, aliskiren (10 or 30 mg/kg per day, 10 weeks) lowered blood pressure, prevented albuminuria, and suppressed renal transforming growth factor-beta and collagen I expression versus vehicle.
31	18490518	In human mesangial cells, aliskiren (0.1 micromol/L to 10 micromol/L) did not inhibit binding of (125)I-renin to the (pro)renin receptor, nor did it alter the activation of extracellular signal-regulated kinase 1/2 by renin (20 nmol/L) preincubated with aliskiren (100 nmol/L) or affect gene expression of the (pro)renin receptor.
32	18490518	The evidence that aliskiren can reduce in vivo gene expression for the (pro)renin receptor and that it may block prorenin-induced angiotensin generation supports the need for additional work to reveal the mechanism of the observed renoprotection by this renin inhibitor.
33	18922597	The binding of prorenin to the (pro)renin receptor triggers two major pathways: the angiotensin II-dependent pathway as a result of the conversion of prorenin to the active form of prorenin through a conformational change, and the angiotensin II-independent, (pro)renin-receptor-dependent intracellular mitogen-activated protein kinase pathway.
34	18922597	The handle region peptide significantly inhibited the development of end-organ damage in these diabetic animals, and had a greater benefit than angiotensin-converting enzyme inhibitors in diabetic angiotensin II-type 1a-receptor-deficient mice.
35	18938683	Discovery of prorenin/renin, or (pro)renin, receptor uncovered a novel function of (pro)renin as receptor ligand in addition to enzyme and its precursor; the same receptor was shown to promote reversible activation of prorenin and enhance the enzyme activity of mature renin.
36	18938683	Its infusion in animal models of hypertension and diabetes not only prevented nephropathy and cardiac hypertrophy, but also caused regression of nephropathy, whereas Ang II receptor gene deletion and angiotensin-converting enzyme inhibition merely delayed the onset or ameliorated pathologic phenotypes.
37	19151536	The bindings of renin and prorenin to the (pro)renin receptor trigger two major pathways: the angiotensin II-dependent pathway as a result of the enzymatic activation of renin/prorenin and the angiotensin II-independent intracellular pathway involving hypertrophic, hyperplastic, and profibrotic signals.
38	19151536	Its infusion in animal models of diabetes and low-renin hypertension significantly inhibited the development and progression of nephropathy, but (pro)renin receptor blockade had no benefit in the clipped kidney of 2K1C rats or rat models of high-renin hypertension.
39	19151536	The bindings of renin and prorenin to the (pro)renin receptor trigger two major pathways: the angiotensin II-dependent pathway as a result of the enzymatic activation of renin/prorenin and the angiotensin II-independent intracellular pathway involving hypertrophic, hyperplastic, and profibrotic signals.
40	19151536	Its infusion in animal models of diabetes and low-renin hypertension significantly inhibited the development and progression of nephropathy, but (pro)renin receptor blockade had no benefit in the clipped kidney of 2K1C rats or rat models of high-renin hypertension.
41	19557706	The binding of prorenin to the (pro)renin receptor triggers 2 major pathways: a nonproteolytic conformational change in prorenin to its active form (angiotensin II-dependent pathway) and an intracellular pathway via the (pro)renin receptor itself (angiotensin II-independent pathway).
42	19557706	Thus, the administration of a "handle" region peptide (HRP), which acts as a decoy peptide and competitively inhibits the binding of prorenin to the (pro)renin receptor, has a beneficial effect in the kidneys of diabetic animals with low plasma renin levels.
43	19557706	The binding of prorenin to the (pro)renin receptor triggers 2 major pathways: a nonproteolytic conformational change in prorenin to its active form (angiotensin II-dependent pathway) and an intracellular pathway via the (pro)renin receptor itself (angiotensin II-independent pathway).
44	19557706	Thus, the administration of a "handle" region peptide (HRP), which acts as a decoy peptide and competitively inhibits the binding of prorenin to the (pro)renin receptor, has a beneficial effect in the kidneys of diabetic animals with low plasma renin levels.
45	19641301	Association of (pro)renin receptor mRNA expression with angiotensin-converting enzyme mRNA expression in human artery.
46	19769609	(Pro)renin receptor (PRR) binding to renin or prorenin mediates angiotensin (Ang) II-dependent and -independent effects.
47	19769609	The urine albumin : creatinine ratio (UACR), renal interstitial fluid (RIF) levels of AngII, TNF-alpha and IL-1beta and renal expression of TNF-alpha and IL-1beta were evaluated in control, untreated diabetic and diabetic rats treated with either a PRR blocker (PRRB; 0.2 mg/kg per day NH3-RILLKKMPSV-COOH), the AT(1) receptor antagonist valsartan (2 mg/kg per day) or combined therapy, administered directly into the renal cortical interstitium for 14 days via osmotic minipumps. 3.
48	19769609	Compared with values in normoglycaemic control rats, UACR and RIF AngII, TNF-alpha and IL-1beta were significantly higher in untreated diabetic rats.
49	19769609	Treatment of diabetic rats with the PRRB or valsartan alone and in combination significantly reduced UACR and RIF TNF-alpha and IL-1beta levels.
50	19769609	Renal expression of TNF-alpha and IL-1beta was higher in untreated diabetic rats than in control rats, but was reduced significantly following treatment with PRRB or valsartan alone and in combination.
51	19769609	The PRRB had no effect on RIF AngII levels, whereas valsartan alone and in combination with the PRRB significantly increased AngII levels. 4.
52	19769609	In conclusion, the PRR is involved in the development and progression of kidney disease in diabetes by enhancing renal production of the inflammatory cytokines TNF-alpha and IL-1beta, independent of renal AngII effects.
53	20444941	Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways.
54	20444941	Renal (pro)renin receptor (PRR) expression is increased in diabetes.
55	20444941	We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways.
56	20444941	Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63).
57	20444941	By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription.
58	20444941	Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation.
59	20444941	Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63).
60	20444941	GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536).
61	20444941	SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63).
62	20444941	We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways.
63	20444941	NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells.
64	20444941	Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways.
65	20444941	Renal (pro)renin receptor (PRR) expression is increased in diabetes.
66	20444941	We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways.
67	20444941	Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63).
68	20444941	By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription.
69	20444941	Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation.
70	20444941	Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63).
71	20444941	GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536).
72	20444941	SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63).
73	20444941	We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways.
74	20444941	NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells.
75	21177830	Recent data suggest that nicotinamide adenine dinucleotide phosphate oxidase-mediated oxidative injury to the proximal tubule, like that seen in the glomerulus, contributes to proteinuria in insulin-resistant states.
76	21177830	The vasodilator β-blocker nebivolol reduces nicotinamide adenine dinucleotide phosphate oxidase activity, increases bioavailable nitric oxide, and improves insulin sensitivity.
77	21177830	Compared with Zucker lean, ZO controls exhibited increased proteinuria and γ-glutamyl transpeptidase, reductions in systemic insulin sensitivity in association with increased renal renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid receptor immunostaining, oxidative stress, and glomerular tubular structural abnormalities that were substantially improved with in vivo nebivolol treatment.
78	21177830	Nebivolol treatment also led to improvements in glomerular podocyte foot-process effacement and improvement in podocyte-specific proteins (nephrin and synaptopodin) as well as proximal tubule-specific proteins (megalin and lysosomal-associated membrane protein-2) and proximal tubule ultrastructural remodeling in the ZO kidney.
79	21737546	Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression.
80	21737546	In cultured podocytes overexpressing COX-2, high glucose induced cell injury and increased both expression of the pro(renin) receptor and activation of the renin-angiotensin system.
81	21737546	In vivo, podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot-process effacement, and mesangial matrix expansion.
82	21737546	In summary, these results demonstrate that increased expression of podocyte COX-2 predisposes to diabetic glomerular injury and that the (pro)renin receptor may be one mediator for this increased susceptibility to injury.
83	21737546	Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression.
84	21737546	In cultured podocytes overexpressing COX-2, high glucose induced cell injury and increased both expression of the pro(renin) receptor and activation of the renin-angiotensin system.
85	21737546	In vivo, podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot-process effacement, and mesangial matrix expansion.
86	21737546	In summary, these results demonstrate that increased expression of podocyte COX-2 predisposes to diabetic glomerular injury and that the (pro)renin receptor may be one mediator for this increased susceptibility to injury.
87	21737546	Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression.
88	21737546	In cultured podocytes overexpressing COX-2, high glucose induced cell injury and increased both expression of the pro(renin) receptor and activation of the renin-angiotensin system.
89	21737546	In vivo, podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot-process effacement, and mesangial matrix expansion.
90	21737546	In summary, these results demonstrate that increased expression of podocyte COX-2 predisposes to diabetic glomerular injury and that the (pro)renin receptor may be one mediator for this increased susceptibility to injury.
91	21737546	Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression.
92	21737546	In cultured podocytes overexpressing COX-2, high glucose induced cell injury and increased both expression of the pro(renin) receptor and activation of the renin-angiotensin system.
93	21737546	In vivo, podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot-process effacement, and mesangial matrix expansion.
94	21737546	In summary, these results demonstrate that increased expression of podocyte COX-2 predisposes to diabetic glomerular injury and that the (pro)renin receptor may be one mediator for this increased susceptibility to injury.
95	21945916	The rate limiting enzyme is renin, which in the circulating RAS derives from the kidney to generate Ang II, which in turn regulates cardiovascular function by binding to AT(1) and AT(2) receptors on cardiac, renal and vascular cells.
96	21945916	Whereas angiotensinsinogen, angiotensin converting enzyme (ACE), Ang I and Ang II are synthesized within these tissues, there is still controversy as to whether renin is produced locally or whether it is taken up from the circulation, possibly by the (pro)renin receptor.
97	21945916	New concepts relating to the vascular RAS have recently been elucidated including: (1) the presence of functionally active Ang-(1-7)-Mas axis in the vascular system, (2) the importance of the RAS in perivascular adipose tissue and cross talk with vessels, and (3) the contribution to vascular RAS of Ang II derived from immune and inflammatory cells within the vascular wall.
98	22684035	(Pro)renin receptor and insulin resistance: possible roles of angiotensin II-dependent and -independent pathways.
99	22684035	In this regard, our preliminary data showed that the development of insulin resistance was associated with nonproteolytic activation of prorenin as well as local angiotensin II generation in skeletal muscle and adipose tissues of obese Otsuka Long-Evans Tokushima Fatty rats.
100	22684035	In fructose-fed rats, insulin resistance was also associated with nonproteolytic activation of prorenin and skeletal muscle angiotensin II generation.
101	23934056	The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril.
102	23934056	However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice.