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Wnt/β-catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC6 in podocytes.
MedLine Citation:
PMID:  23294354     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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 (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.
RESULTS: 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.
CONCLUSION: These findings indicate that the Wnt/β-catenin signalling pathway may potentially be active in pathogenesis of TRPC6-mediated diabetic podocyte injury.
Authors:
Z Li; J Xu; P Xu; S Liu; Z Yang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell proliferation     Volume:  46     ISSN:  1365-2184     ISO Abbreviation:  Cell Prolif.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  76-85     Citation Subset:  IM    
Copyright Information:
© 2013 Blackwell Publishing Ltd.
Affiliation:
Department of Physiology, College of Medicine, Nankai University, 300071, Tianjin, China.
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