title: Wnt/β-catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC6 in podocytes.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These findings indicate that the Wnt/β-catenin signalling pathway may potentially be active in pathogenesis of TRPC6-mediated diabetic podocyte injury.
authors.affiliation: Department of Physiology, College of Medicine, Nankai University, 300071, Tianjin, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: P
authors.initials: P
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000494:pharmacology*; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D013997:Time Factors; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D005947:Glucose