title: Changes of podocyte p130Cas in diabetic conditions.
abstract: BACKGROUND
  Proteinuria results from increased glomerular permeability and is associated with retraction and effacement of the highly specialized interdigitating podocyte foot processes. In podocytes (glomerular epithelial cells [GECs]), p130Cas localizes diffusely to the cytoplasm and connects focal adhesion proteins and kinases to the glomerular basement membrane and adapter proteins of slit diaphragm insertion sites.
  
  
  METHODS
  To investigate whether high-glucose (HG) and advanced glycosylation end products (AGEs) induce quantitative and distributional changes of podocyte p130Cas protein, a docking protein connecting F-actin fibers to the glomerular basement membrane and adapter proteins, we cultured rat GECs (r-GECs) and mouse GECs (m-GECs) under (i) normal glucose (5 mM = control), (ii) HG (30 mM), (iii) AGE-added or (iv) HG plus AGE-added conditions. We also prepared streptozotocin-induced diabetic renal tissues.
  
  
  RESULTS
  We found that p130Cas stainings were located in peripheral cytoplasm of r-GECs and m-GECs as dots in linear alignment, partially colocalized with actin-binding proteins such as synaptopodin and alpha-actinin, and locally connected to the ends of actin filaments. In diabetic conditions, the intensities of p130Cas stainings were diminished in more pathological HG plus AGE-added condition of r-GECs and m-GECs and in chronic diabetic renal tissues. p130Cas protein was decreased significantly by HG, AGE and HG plus AGE in both cells compared with normal glucose or osmotic control conditions. p130Cas mRNA expression levels were also suppressed similarly in diabetic conditions.
  
  
  CONCLUSIONS
  We suggest that diabetic conditions modulate the quantitative and distributional changes of podocyte p130Cas and therefore affect the filtration function of podocytes.
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju - Korea.
authors.forename: Tae-Sun
authors.initials: TS
authors.lastname: Ha
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Gi-Dong
authors.initials: GD
authors.lastname: Han
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
chemical_list: D000199:Actins; D050719:Crk-Associated Substrate Protein; D017127:Glycation End Products, Advanced; D008840:Microfilament Proteins; D012333:RNA, Messenger; C503968:Synpo protein, mouse; C551863:Synpo2l protein, rat