title: Effect of simvastatin on expression of transforming growth factor-β and collagen type IV in rat mesangial cells.
abstract: OBJECTIVE
  Diabetic nephropathy is characterized by the accumulation of extracellular matrix in the glomerular mesangium as a result of an imbalance between matrix synthesis and degradation. Since simvastatin has been proposed to decrease renal interstitial fibrosis, we hypothesized that the protective effect of statins was related to the expression of transforming growth factor-β (TGF-β) and type IV collagen (Col IV).
  
  
  METHODS
  Cultured rat mesangial cells (RMC) were exposed to high glucose (HG), advanced glycosylation end products (AGE) or H(2)O(2) in the absence and presence of simvastatin. Expression of TGF-β and Col IV was determined by Western blotting.
  
  
  RESULTS
  Coincubation of RMC with HG, AGE or H(2)O(2) resulted in a significant increase of the expression of TGF-β and Col IV (p < 0.05). Simvastatin significantly inhibited HG-, AGE- or H(2)O(2)-induced expression of TGF-β and Col IV (p < 0.05). Moreover, simvastatin also inhibited HG-, AGE- and H(2)O(2)-induced activation of p38 mitogen-activated protein kinase, which indicated that the preventive effect of simvastatin on TGF-β and Col IV may be associated with p38.
  
  
  CONCLUSIONS
  These findings suggest that simvastatin can reduce HG-, AGE- and H(2)O(2)-induced expression of TGF-β and Col IV by inhibition of the p38 pathway.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, China. liyanbohyd@hotmail.com
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Li
authors.forename: Jia-Jing
authors.initials: JJ
authors.lastname: Yin
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D019821:Simvastatin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D017127:Glycation End Products, Advanced; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D016212:Transforming Growth Factor beta; D019821:Simvastatin; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580