Wnt/β-catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC6 in podocytes
Article first published online: 7 JAN 2013
© 2013 Blackwell Publishing Ltd
Volume 46, Issue 1, pages 76–85, February 2013
How to Cite
Li, Z., Xu, J., Xu, P., Liu, S. and Yang, Z. (2013), Wnt/β-catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC6 in podocytes. Cell Proliferation, 46: 76–85. doi: 10.1111/cpr.12010
- Issue published online: 7 JAN 2013
- Article first published online: 7 JAN 2013
- Manuscript Accepted: 26 AUG 2012
- Manuscript Received: 21 MAY 2012
- National Basic Research Program of China. Grant Number: 2011CB944003
- National Natural Science Foundation of China. Grant Number: 31070890
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.
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.
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.
These findings indicate that the Wnt/β-catenin signalling pathway may potentially be active in pathogenesis of TRPC6-mediated diabetic podocyte injury.