High Glucose Induces Podocyte Injury Via Enhanced (pro)renin Receptor-Wnt-β-catenin-snail Signaling Pathway

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Feb 18

PMID 24533170

Citations 47

Authors

Caixia Li

Helmy M Siragy

Affiliations

Soon will be listed here.

Abstract

(Pro)renin receptor (PRR) expression is upregulated in diabetes. We hypothesized that PRR contributes to podocyte injury via activation of Wnt-β-catenin-snail signaling pathway. Mouse podocytes were cultured in normal (5 mM) or high (25 mM) D-glucose for 3 days. Compared to normal glucose, high glucose significantly decreased mRNA and protein expressions of podocin and nephrin, and increased mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail, respectively. Confocal microscopy studies showed significant reduction in expression and reorganization of podocyte cytoskeleton protein, F-actin, in response to high glucose. Transwell functional permeability studies demonstrated significant increase in albumin flux through podocytes monolayer with high glucose. Cells treated with high glucose and PRR siRNA demonstrated significantly attenuated mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail; enhanced expressions of podocin mRNA and protein, improved expression and reorganization of F-actin, and reduced transwell albumin flux. We conclude that high glucose induces podocyte injury via PRR-Wnt-β-catenin-snail signaling pathway.

Citing Articles

Cardiovascular effect of preeclampsia upon offspring development: Are (Pro) renin-renin receptor ((P)RR) and gender related?.

Baeza-Perez L, Cabrera-Becerra S, Romero-Nava R, Ramos-Tovar E, Hernandez-Campos M, Lopez-Sanchez P Iran J Basic Med Sci. 2024; 27(5):621-629.

PMID: 38629095 PMC: 11017840. DOI: 10.22038/IJBMS.2024.72486.15790.

Renal Expression and Localization of the Receptor for (Pro)renin and Its Ligands in Rodent Models of Diabetes, Metabolic Syndrome, and Age-Dependent Focal and Segmental Glomerulosclerosis.

Iacobini C, Vitale M, Sentinelli F, Haxhi J, Pugliese G, Menini S Int J Mol Sci. 2024; 25(4).

PMID: 38396894 PMC: 10888662. DOI: 10.3390/ijms25042217.

Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells.

Tsang T, Wiese M, Helmstadter M, Stehle T, Seyfferth J, Shvedunova M Sci Adv. 2023; 9(34):eadh5598.

PMID: 37624894 PMC: 10456878. DOI: 10.1126/sciadv.adh5598.

Differential Methylation of Telomere-Related Genes Is Associated with Kidney Disease in Individuals with Type 1 Diabetes.

Hill C, Duffy S, Kettyle L, McGlynn L, Sandholm N, Salem R Genes (Basel). 2023; 14(5).

PMID: 37239390 PMC: 10217816. DOI: 10.3390/genes14051029.

RAGE is a critical factor of sex-based differences in age-induced kidney damage.

Bajwa S, Luebbe A, Vo N, Piskor E, Kosan C, Wolf G Front Physiol. 2023; 14:1154551.

PMID: 37064891 PMC: 10090518. DOI: 10.3389/fphys.2023.1154551.

References

Ueno K, Hirata H, Majid S, Tabatabai Z, Hinoda Y, Dahiya R . IGFBP-4 activates the Wnt/beta-catenin signaling pathway and induces M-CAM expression in human renal cell carcinoma. Int J Cancer. 2011; 129(10):2360-9. DOI: 10.1002/ijc.25899. View

Hsu R, Ho J, Cha T, Yu D, Wu C, Huang W . WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/β-catenin pathway. PLoS One. 2012; 7(10):e47649. PMC: 3477117. DOI: 10.1371/journal.pone.0047649. View

Huang J, Siragy H . Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways. Endocrinology. 2010; 151(7):3317-25. PMC: 2903935. DOI: 10.1210/en.2009-1368. View

Cheng H, Fan X, Moeckel G, Harris R . Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression. J Am Soc Nephrol. 2011; 22(7):1240-51. PMC: 3137572. DOI: 10.1681/ASN.2010111149. View

Ikenouchi J, Matsuda M, Furuse M, Tsukita S . Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci. 2003; 116(Pt 10):1959-67. DOI: 10.1242/jcs.00389. View

Dai C, Stolz D, Kiss L, Monga S, Holzman L, Liu Y . Wnt/beta-catenin signaling promotes podocyte dysfunction and albuminuria. J Am Soc Nephrol. 2009; 20(9):1997-2008. PMC: 2736766. DOI: 10.1681/ASN.2009010019. View

Matsui I, Ito T, Kurihara H, Imai E, Ogihara T, Hori M . Snail, a transcriptional regulator, represses nephrin expression in glomerular epithelial cells of nephrotic rats. Lab Invest. 2007; 87(3):273-83. DOI: 10.1038/labinvest.3700518. View

Tryggvason K, Patrakka J, Wartiovaara J . Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006; 354(13):1387-401. DOI: 10.1056/NEJMra052131. View

Philipp I, Aufschnaiter R, Ozbek S, Pontasch S, Jenewein M, Watanabe H . Wnt/beta-catenin and noncanonical Wnt signaling interact in tissue evagination in the simple eumetazoan Hydra. Proc Natl Acad Sci U S A. 2009; 106(11):4290-5. PMC: 2646623. DOI: 10.1073/pnas.0812847106. View

10.

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

11.

Terada Y, Tanaka H, Okado T, Shimamura H, Inoshita S, Kuwahara M . Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats. J Am Soc Nephrol. 2003; 14(5):1223-33. DOI: 10.1097/01.asn.0000060577.94532.06. View

12.

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

13.

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

14.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

15.

Nelson P, von Toerne C, Grone H . Wnt-signaling pathways in progressive renal fibrosis. Expert Opin Ther Targets. 2011; 15(9):1073-83. DOI: 10.1517/14728222.2011.588210. View

16.

Lewis E, Hunsicker L, Clarke W, Berl T, Pohl M, Lewis J . Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001; 345(12):851-60. DOI: 10.1056/NEJMoa011303. View

17.

Waters A, Koziell A . Activation of canonical Wnt signaling meets with podocytopathy. J Am Soc Nephrol. 2009; 20(9):1864-6. PMC: 3099395. DOI: 10.1681/ASN.2009070762. View

18.

Xue C, Siragy H . Local renal aldosterone system and its regulation by salt, diabetes, and angiotensin II type 1 receptor. Hypertension. 2005; 46(3):584-90. DOI: 10.1161/01.HYP.0000175814.18550.c0. View

19.

Wang D, Dai C, Li Y, Liu Y . Canonical Wnt/β-catenin signaling mediates transforming growth factor-β1-driven podocyte injury and proteinuria. Kidney Int. 2011; 80(11):1159-1169. PMC: 4300105. DOI: 10.1038/ki.2011.255. View

20.

Nguyen G, Contrepas A . Physiology and pharmacology of the (pro)renin receptor. Curr Opin Pharmacol. 2008; 8(2):127-32. DOI: 10.1016/j.coph.2007.12.009. View