title: Osthole regulates TGF-β1 and MMP-2/9 expressions via activation of PPARα/γ in cultured mouse cardiac fibroblasts stimulated with angiotensin II.
abstract: OBJECTIVE
  Our previous studies have demonstrated that osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, can prevent isoprenaline-induced myocardial fibrosis in mice, but the underlying mechanism is still unclear.
  
  
  METHODS
  The mouse cardiac fibroblasts (CFs) stimulated with angiotensin II (Ang II) were cultured and treated with different concentrations of osthole. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α/γ, transforming growth factor β1 (TGF-β1), and matrix metalloproteinase (MMP)-2/9 were detected by reverse transcription polymerase chain reaction method, and the protein expressions of nuclear factor-κB (NF-κB) and TGF-β1 were detected by Western blot method, respectively.
  
  
  RESULTS
  Following treatment of cells with osthole at 2.5, 5, 10 and 20 μg/mL, the NF-κB and TGF-β1 expressions were dose-dependently decreased, while the expressions of PPARα/γ and MMP-2/9 were dose-dependently increased. After the cells were preincubated with PPARα antagonist (MK886) or/and PPARγ antagonist (GW9662), the inhibitions of osthole on the NF-κB and TGF-β1 expressions were decreased or completely halted and the increment of osthole on the MMP-2/9 expressions were also decreased or completely cancelled.
  
  
  CONCLUSIONS
  Osthole could inhibit the NF-κB and TGF-β1 expressions by activation of PPARα/γ, and subsequently enhance the MMP-2/9 expressions in cultured CFs, and these effects of osthole may play the beneficial roles in the prevention and treatment of myocardial fibrosis.
authors.affiliation: Soochow University.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
authors.forename: Meilin
authors.initials: M
authors.lastname: Xie
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D009206:Myocardium / Q000166:cytology; D016328:NF-kappa B / Q000235:genetics; D047493:PPAR alpha / Q000037:antagonists & inhibitors / Q000235:genetics*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D003374:Coumarins; D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C046627:osthol