title: Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression.
abstract: OBJECTIVE
  Podocytes injury is involved in the development of diabetic nephropathy. This study was designed to confirm the reno- and podocyte-protective effects of pitavastatin in diabetic rats and clarify its mechanisms.
  
  
  METHODS
  Wistar rats were divided into 4 treatment groups: control, streptozotocin (STZ; 55 mg/kg)-induced diabetes, STZ with pitavastatin (10 mg/kg/day), and STZ with tempol (1 mmol/l).
  
  
  RESULTS
  STZ-induced diabetic rats exhibited increases in urinary protein excretion and plasma creatinine, and a decrease in creatinine clearance. Pitavastatin significantly improved these parameters without reducing cholesterol levels, whereas tempol did not. The treatment with STZ-enhanced renal fibrosis, mesangial proliferation, transforming growth factor (TGF)-β, MCP-1 and suppressed Rho in association with decrement of bone morphogenetic protein (BMP)-7 expression in renal cortex. Moreover, STZ decreased podocyte related factors, podocin and nephrin, and BMP-7 in podocytes. Pitavastatin significantly ameliorated all these indices. On the other hand, improvement by tempol was found only in TGF-β, MCP-1 and histological changes.
  
  
  CONCLUSIONS
  Pitavastatin exhibited reno- and podocyte-protective effects accompanied by BMP-7 preservation and Rho suppression.
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohigashi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Imai
authors.forename: Hiroe
authors.initials: H
authors.lastname: Toba
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakata
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D009566:Nitrates; D009573:Nitrites; D020011:Protective Agents; D011804:Quinolines; D016212:Transforming Growth Factor beta; C113267:nephrin; D008315:Malondialdehyde; D003404:Creatinine; D054460:rho-Associated Kinases; C108475:pitavastatin