Wnt/β‐catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC6 in podocytes. (7th January 2013)

• Record Type: Journal Article
• Authors: Li, Z.; Xu, J.; Xu, P.; Liu, S.; Yang, Z.
• Is Part Of: Cell proliferation. Volume 46:Number 1(2013:Feb.)
• Page Start: 76
• Page End: 85
• Publication Date: 2013-01-07
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12010
• Languages: English
• ISSNs: 0960-7722

Abstract

<abstract abstract-type="main" xml:lang="en" id="cpr12010-abs-0001"> <title>Abstract</title> <sec id="cpr12010-sec-0001" sec-type="section"> <title>Objectives</title> <p>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 (TRPC6), which is regulated by the canonical Wnt signalling pathway, in mouse podocytes.</p> </sec> <sec id="cpr12010-sec-0002" sec-type="section"> <title>Materials and methods</title> <p>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.</p> </sec> <sec id="cpr12010-sec-0003" sec-type="section"> <title>Results</title> <p>HG induced apoptosis and reduced viability of differentiated podocytes. It caused time‐dependent up‐regulation of TRPC6 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 TRPC6 up‐regulation and amelioration of podocyte apoptosis. Furthermore, reduction of cell viability induced by HG was attenuated by treatment with Dkk1.</p> </sec> <sec id="cpr12010-sec-0004" sec-type="section"> <title>Conclusion</title> <p>These findings indicate that the Wnt/β‐catenin signalling pathway may potentially be active in pathogenesis of TRPC6‐mediated diabetic podocyte injury.</p> </sec> </abstract>