Open AccessWnt/β‐catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC 6 in podocytes
Author(s) -
Li Z.,
Xu J.,
Xu P.,
Liu S.,
Yang Z.
Publication year - 2013
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12010
Subject(s) - podocyte , wnt signaling pathway , microbiology and biotechnology , diabetic nephropathy , dkk1 , lrp5 , biology , cancer research , signal transduction , endocrinology , diabetes mellitus , kidney , proteinuria
Abstract Objectives Diabetic nephropathy is a major complication of diabetes and a frequent cause of end‐stage renal disease and recent studies suggest that podocyte damage may play a role in the pathogenesis of this. At early onset of diabetic nephropathy there is podocyte drop‐out, which is thought to provoke glomerular albuminuria and subsequent glomerular injury; however, the underlying molecular mechanisms of this remain poorly understood. Here we report that we tested the hypothesis that early diabetic podocyte injury is caused, at least in part, by up‐regulation of transient receptor potential cation channel 6 ( TRPC 6), which is regulated by the canonical Wnt signalling pathway, in mouse podocytes. Materials and methods Mechanism of injury initiation in mouse podocytes, by high concentration of D‐glucose (HG, 30 mM ), was investigated by MTT, flow cytometry, real‐time quantitative PCR, and western blot analysis. Results HG induced apoptosis and reduced viability of differentiated podocytes. It caused time‐dependent up‐regulation of TRPC 6 and activation of the canonical Wnt signalling pathway, in mouse podocytes. In these cells, blockade of the Wnt signalling pathway by dickkopf related protein 1 (Dkk1) resulted in effective reduction of TRPC 6 up‐regulation and amelioration of podocyte apoptosis. Furthermore, reduction of cell viability induced by HG was attenuated by treatment with Dkk1. Conclusion These findings indicate that the Wnt/β‐catenin signalling pathway may potentially be active in pathogenesis of TRPC 6‐mediated diabetic podocyte injury.