High Glucose Induces Podocyte Injury via Enhanced (Pro)renin Receptor-Wnt-β-Catenin-Snail Signaling Pathway

被引：58

作者：

Li, Caixia ^{[1
]}

Siragy, Helmy M. ^{[1
]}

机构：

[1] Univ Virginia Hlth Syst, Div Endocrinol & Metab, Charlottesville, VA 22903 USA

来源：

PLOS ONE | 2014年 / 9卷 / 02期

基金：

美国国家卫生研究院;

关键词：

PRO RENIN RECEPTOR; TO-MESENCHYMAL TRANSITION; VACUOLAR H+-ATPASE; WNT/BETA-CATENIN; PRORENIN RECEPTOR; KIDNEY-DISEASE; DIABETIC-NEPHROPATHY; UP-REGULATION; RENAL INJURY; EXPRESSION;

D O I：

10.1371/journal.pone.0089233

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

(Pro)renin receptor (PRR) expression is upregulated in diabetes. We hypothesized that PRR contributes to podocyte injury via activation of Wnt-beta-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, beta-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, beta-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- beta-catenin- snail signaling pathway.

引用

页数：8

共 49 条

[1] The (Pro) Renin Receptor Site-Specific and Functional Linkage to the Vacuolar H+-ATPase in the Kidney [J].

Advani, Andrew ;

Kelly, Darren J. ;

Cox, Alison J. ;

White, Kathryn E. ;

Advani, Suzanne L. ;

Thai, Kerri ;

Connelly, Kim A. ;

Yuen, Darren ;

Trogadis, Judy ;

Herzenberg, Andrew M. ;

Kuliszewski, Michael A. ;

Leong-Poi, Howard ;

Gilbert, Richard E. .

HYPERTENSION, 2009, 54 (02) :261-U129

[2] Activation of adenosine 2A receptors preserves structure and function of podocytes [J].

Awad, Alaa S. ;

Rouse, Michael ;

Liu, Lixia ;

Vergis, Amy L. ;

Rosin, Diane L. ;

Linden, Joel ;

Sedor, John R. ;

Okusa, Mark D. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2008, 19 (01) :59-68

[3] Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney [J].

Boutet, Agnes ;

De Frutos, Cristina A. ;

Maxwell, Patrick H. ;

Mayol, M. Jose ;

Romero, J. ;

Nieto, M. Angela .

EMBO JOURNAL, 2006, 25 (23) :5603-5613

[4] Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy [J].

Brenner, BM ;

Cooper, ME ;

de Zeeuw, D ;

Keane, WF ;

Mitch, WE ;

Parving, HH ;

Remuzzi, G ;

Snapinn, SM ;

Zhang, ZX ;

Shahinfar, S .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (12) :861-869

[5] The intrarenal renin-angiotensin system and diabetic nephropathy [J].

Carey, RM ;

Siragy, HM .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2003, 14 (06) :274-281

[6] Podocyte COX-2 Exacerbates Diabetic Nephropathy by Increasing Podocyte (Pro)renin Receptor Expression [J].

Cheng, Huifang ;

Fan, Xiaofeng ;

Moeckel, Gilbert W. ;

Harris, Raymond C. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 22 (07) :1240-1251

[7] Wnt/β-catenin signaling in development and disease [J].

Clevers, Hans .

CELL, 2006, 127 (03) :469-480

[8] Wnt/β-Catenin Signaling and Disease [J].

Clevers, Hans ;

Nusse, Roel .

CELL, 2012, 149 (06) :1192-1205

[9] Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes [J].

Coimbra, TM ;

Janssen, U ;

Gröne, HJ ;

Ostendorf, T ;

Kunter, U ;

Schmidt, H ;

Brabant, G ;

Floege, J .

KIDNEY INTERNATIONAL, 2000, 57 (01) :167-182

[10] Chronic high glucose downregulates mitochondrial calpain 10 and contributes to renal cell death and diabetes-induced renal injury [J].

Covington, Marisa D. ;

Schnellmann, Rick G. .

KIDNEY INTERNATIONAL, 2012, 81 (04) :391-400

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