title: Wogonin inhibits transforming growth factor β1-induced extracellular matrix production via the p38/activator protein 1 signaling pathway in nasal polyp-derived fibroblasts.
abstract: BACKGROUND
  Wogonin has been shown to have antifibrotic and anti-inflammatory effects in the lower airway. The purpose of this study was to evaluate the effects of wogonin on transforming growth factor (TGF) β1-induced myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction, and to determine the molecular mechanisms of wogonin in nasal polyp-derived fibroblasts (NPDF).
  
  
  METHODS
  NPDFs were isolated from nasal polyps from eight patients. TGF-β1-induced NPDFs were treated with wogonin. Cytotoxicity was evaluated by using a 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Fibroblast migration was evaluated with transwell and scratch migration assays. The expression levels of α-smooth muscle actin, fibronectin, phosphorylated-p38, and c-Fos were determined by Western blot and/or reverse transcription-polymerase chain reaction. The total collagen amount was analyzed with the Sircol collagen assay, and contractile activity was measured by a collagen gel contraction assay.
  
  
  RESULTS
  Wogonin (0-60 μM) had no significant cytotoxic effects on TGF-β1-induced NPDFs. Migration of NPDFs was significantly inhibited by wogonin treatment. The expression levels of α-smooth muscle actin and fibronectin were significantly reduced in wogonin-treated NPDFs. Collagen production and contraction were also significantly decreased by wogonin treatment. Wogonin markedly inhibited activation of the p38/activator protein 1 pathway in TGF-β1-induced NPDFs.
  
  
  CONCLUSIONS
  These results indicated that wogonin may inhibit TGF-β1-induced myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction through the p38/activator protein-1 pathway in NPDFs.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Nam Hyoung
authors.initials: NH
authors.lastname: Ryu
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Shin
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Um
authors.forename: Il-Ho
authors.initials: IH
authors.lastname: Park
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects; D009298:Nasal Polyps / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D044950:Flavanones; D018808:Transcription Factor AP-1; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C085514:wogonin