Regulation of (pro)renin Receptor Expression by Glucose-induced Mitogen-activated Protein Kinase, Nuclear Factor-kappaB, and Activator Protein-1 Signaling Pathways

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2010 May 7

PMID 20444941

Citations 35

Authors

Jiqian Huang

Helmy M Siragy

Affiliations

Soon will be listed here.

Abstract

Renal (pro)renin receptor (PRR) expression is increased in diabetes. The exact mechanisms involved in this process are not well established. 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. 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). 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. 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. Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63). GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536). SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63). 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. NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells.

Citing Articles

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References

Babazono T, Dlugosz J, Whiteside C . Altered expression and subcellular localization of diacylglycerol-sensitive protein kinase C isoforms in diabetic rat glomerular cells. Diabetes. 1998; 47(4):668-76. DOI: 10.2337/diabetes.47.4.668. View

Ichihara A, Sakoda M, Kurauchi-Mito A, Kaneshiro Y, Itoh H . Involvement of (pro)renin receptor in the glomerular filtration barrier. J Mol Med (Berl). 2008; 86(6):629-35. PMC: 2374882. DOI: 10.1007/s00109-008-0327-1. View

Kaneshiro Y, Ichihara A, Sakoda M, Takemitsu T, Nabi A, Uddin M . Slowly progressive, angiotensin II-independent glomerulosclerosis in human (pro)renin receptor-transgenic rats. J Am Soc Nephrol. 2007; 18(6):1789-95. DOI: 10.1681/ASN.2006091062. View

Chiao P, Miyamoto S, Verma I . Autoregulation of I kappa B alpha activity. Proc Natl Acad Sci U S A. 1994; 91(1):28-32. PMC: 42879. DOI: 10.1073/pnas.91.1.28. View

Ichihara A, Hayashi M, Kaneshiro Y, Suzuki F, Nakagawa T, Tada Y . Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin. J Clin Invest. 2004; 114(8):1128-35. PMC: 522242. DOI: 10.1172/JCI21398. View

Ludwig J, Kerscher S, Brandt U, Pfeiffer K, Getlawi F, Apps D . Identification and characterization of a novel 9.2-kDa membrane sector-associated protein of vacuolar proton-ATPase from chromaffin granules. J Biol Chem. 1998; 273(18):10939-47. DOI: 10.1074/jbc.273.18.10939. View

Takahashi H, Ichihara A, Kaneshiro Y, Inomata K, Sakoda M, Takemitsu T . Regression of nephropathy developed in diabetes by (Pro)renin receptor blockade. J Am Soc Nephrol. 2007; 18(7):2054-61. DOI: 10.1681/ASN.2006080820. View

Park C, Lee J, Yang C . Curcumin derivatives inhibit the formation of Jun-Fos-DNA complex independently of their conserved cysteine residues. J Biochem Mol Biol. 2005; 38(4):474-80. DOI: 10.5483/bmbrep.2005.38.4.474. View

Ingram A, Ly H, Thai K, Kang M, Scholey J . Mesangial cell signaling cascades in response to mechanical strain and glucose. Kidney Int. 1999; 56(5):1721-8. DOI: 10.1046/j.1523-1755.1999.00743.x. View

10.

Whiteside C, Dlugosz J . Mesangial cell protein kinase C isozyme activation in the diabetic milieu. Am J Physiol Renal Physiol. 2002; 282(6):F975-80. DOI: 10.1152/ajprenal.00014.2002. View

11.

Huang Y, Wongamorntham S, Kasting J, McQuillan D, Owens R, Yu L . Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney Int. 2005; 69(1):105-13. DOI: 10.1038/sj.ki.5000011. View

12.

Demirci F, White N, Rigatti B, LEWIS K, Gorin M . Identification, genomic structure, and screening of the vacuolar proton-ATPase membrane sector-associated protein M8-9 gene within the COD1 critical region (Xp11.4). Mol Vis. 2001; 7:234-9. View

13.

Nguyen G, Delarue F, Burckle C, Bouzhir L, Giller T, Sraer J . Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 2002; 109(11):1417-27. PMC: 150992. DOI: 10.1172/JCI14276. View

14.

Carey R, Siragy H . The intrarenal renin-angiotensin system and diabetic nephropathy. Trends Endocrinol Metab. 2003; 14(6):274-81. DOI: 10.1016/s1043-2760(03)00111-5. View

15.

Herbert J, Augereau J, Gleye J, Maffrand J . Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun. 1990; 172(3):993-9. DOI: 10.1016/0006-291x(90)91544-3. View

16.

Atiyeh B, Arant Jr B, Henrich W, Seikaly M . In vitro production of angiotensin II by isolated glomeruli. Am J Physiol. 1995; 268(2 Pt 2):F266-72. DOI: 10.1152/ajprenal.1995.268.2.F266. View

17.

Vidotti D, Casarini D, Cristovam P, Leite C, Schor N, Boim M . High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells. Am J Physiol Renal Physiol. 2004; 286(6):F1039-45. DOI: 10.1152/ajprenal.00371.2003. View

18.

Chao M, Chen I, Cheng J . Inhibition of protein kinase C translocation from cytosol to membrane by chelerythrine. Planta Med. 1998; 64(7):662-3. DOI: 10.1055/s-2006-957545. View

19.

Carey R, Siragy H . Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev. 2003; 24(3):261-71. DOI: 10.1210/er.2003-0001. View

20.

Nguyen G, Delarue F, Berrou J, Rondeau E, Sraer J . Specific receptor binding of renin on human mesangial cells in culture increases plasminogen activator inhibitor-1 antigen. Kidney Int. 1996; 50(6):1897-903. DOI: 10.1038/ki.1996.511. View