title: Regulation of protease-activated receptor-1 expression in human buccal fibroblasts stimulated with arecoline.
abstract: BACKGROUND
  The purpose of this study was to compare the major thrombin receptor protease-activated receptor-1 (PAR-1) expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanisms that may lead to induce PAR-1 expression.
  
  
  METHODS
  Thirty OSF and 10 normal buccal mucosa specimens were examined by immunohistochemistry. Buccal mucosal fibroblasts (BMFs) were challenged with arecoline by using Western blot analysis. N-acetyl-L-cysteine (NAC), LY294002, herbimycin A, NS-398, and PD98059 were added to find the possible regulatory mechanisms.
  
  
  RESULTS
  PAR-1 expression was significantly higher in OSF specimens (p < .05). Arecoline was found to elevate PAR-1 expression in a dose-dependent and time-dependent manner (p < .05). The addition of NAC, LY294002, herbimycin A, NS398, and PD98059 markedly inhibited the arecoline-induced PAR-1 expression (p < .05).
  
  
  CONCLUSIONS
  PAR-1 expression is significantly upregulated in areca quid chewing-associated OSF. Arecoline-induced PAR-1 expression was downregulated by NAC, LY294002, herbimycin A, NS398, and PD98059.
authors.affiliation: Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Tsai
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.forename: Fu-Mei
authors.initials: FM
authors.lastname: Huang
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001115:Arecoline / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D018679:Cholinergic Agonists / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009025:Morpholines / Q000494:pharmacology; D009061:Mouth Mucosa / Q000166:cytology*; D009578:Nitrobenzenes / Q000494:pharmacology; D009914:Oral Submucous Fibrosis / Q000201:enzymology*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D009578:Nitrobenzenes; D044463:Receptor, PAR-1; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017828:Rifabutin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D001115:Arecoline; C020754:herbimycin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000111:Acetylcysteine