title: Notoginsenoside R1 ameliorates podocyte adhesion under diabetic condition through α3β1 integrin upregulation in vitro and in vivo.
abstract: BACKGROUND
  Decreased expression of α3β1 integrin may contribute to reduction in podocyte adhesion to glomerular basement membrane (GBM), which represents a novel early mechanism leading to diabetic kidney disease (DKD). Here, we examined the protective effects of Notoginsenoside R1 (NR1) on podocyte adhesion and α3β1 integrin expression under diabetic condition in vitro and in vivo.
  
  
  METHODS
  Conditionally immortalized mouse podocytes were exposed to high glucose (HG) with 10 and 100μg /ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and α3β1 integrin expression were measured in vitro and in vivo.
  
  
  RESULTS
  HG decreased podocyte adhesive capacity and α3β1 integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α3β1 integrin protein and mRNA expression. These in vitro observations were confirmed in vivo. In streptozotocin(STZ)-induced diabetic rats, treatment with NR1 (5 and 10 mg· kg(-1)· d(-1)) for 12 weeks partially restored the number of podocytes per glomerular volume and glomerular α3β1 integrin expression, as well as ameliorated albuminuria, histopathology and oxidative stress. NR1 also inhibited glomerular ILK activity in diabetic rats.
  
  
  CONCLUSIONS
  NR1, a novel antioxidant, ameliorated glucose-induced impaired podocyte adhesive capacity and subsequent podocyte depopulation partly through α3β1 integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Dingkun
authors.initials: D
authors.lastname: Gui
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Guihua
authors.initials: G
authors.lastname: Jian
authors.forename: Yongping
authors.initials: Y
authors.lastname: Guo
authors.forename: Jiajun
authors.initials: J
authors.lastname: Yang
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000008:administration & dosage*; D050533:Glomerular Basement Membrane / Q000187:drug effects / Q000473:pathology; D039201:Integrin alpha3beta1 / Q000096:biosynthesis*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects / Q000473:pathology; D051381:Rats
chemical_list: D036145:Ginsenosides; D039201:Integrin alpha3beta1; C072936:notoginsenoside R1