title: β-catenin and its alteration in an experimental model of diabetic nephropathy.
abstract: BACKGROUND
  The aim of our study was to determine whether beta-catenin, a subunit of the cadherin protein complex in the podocyte cytoskeleton, would be altered by hyperglycemia and advanced glycation endproducts (AGE) in glomerular epithelial cells and podocytes in vitro.
  
  
  METHODS
  Rat glomerular epithelial cells and mouse podocytes on bovine serum albumin-coated or AGE-coated plates with normal (5 mM) and high (30 mM) glucose doses were cultured and examined for the distribution of bet;-catenin using confocal microscopy and changes in beta-catenin production by western blotting and reverse transcription-polymerase chain reaction, at 48 hours, 4 weeks, and 10 weeks.
  
  
  RESULTS
  Immunofluorescent staining revealed that beta-catenin and alpha-actinin were colocalized around the cell membrane, and that beta-catenin staining was most intense along the capillary loops, but moved internally toward the inner actin filaments in the presence of AGE and hyperglycemia. In western blot analysis, AGE and hyperglycemia significantly decreased the amount of beta-catenin proteins by 31.5% at 48 hours, compared with normal control conditions (P = .01). The expression for beta-catenin mRNA in AGE and hyperglycemia was also decreased by 59.6% at 24 hours, compared with that of normal glucose conditions (P = .01). No significant changes were seen in the osmotic controls.
  
  
  CONCLUSIONS
  Our results suggest that AGE and hyperglycemia may induce the cytoplasmic redistribution of beta-catenin and inhibit the production of beta-catenin at the transcriptional and posttranslational levels, which may result in the development of kidney dysfunction in diabetic conditions.
authors.affiliation: Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea. fli018@hanmail.net.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Ahn
authors.forename: Tae-Sun
authors.initials: TS
authors.lastname: Ha
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Shin
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose; D017127:Glycation End Products, Advanced; D006943:Hyperglycemia / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008962:Models, Theoretical; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D051176:beta Catenin; D000185:Actinin; D005947:Glucose