The major thrombin receptor protease-activated receptor-1 (PAR-1) is
consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of
this study was to compare PAR-1 expression in normal human buccal mucosa and
oral submucous fibrosis (OSF) specimens and further explore the potential
mechanism that may lead to induce PAR-1 expression. Thirty OSF specimens and ten
normal buccal mucosa were examined by immunohistochemistry. Primary buccal
mucosal fibroblasts (BMFs) were challenged with arecoline, a major areca nut
alkaloid, by using Western blot analysis. Furthermore, glutathione precursor
N-acetyl-L-cysteine (NAC), phosphatidylinositol 3-kinase (PI3K) inhibitor
LY294002, tyrosine kinase inhibitor herbimycin A, cyclooxygenase-2 inhibitor
NS-398, and extracellular signal-regulated protein kinase (ERK) inhibitor PD98059
were added to find the possible regulatory mechanisms. PAR-1 expression was
significantly higher in OSF specimens (p<0.05) and expressed mainly by fibroblasts
and inflammatory cells. Arecoline was found to elevate PAR-1 expression in a doseand
time-dependent manner (p<0.05). The addition of NAC, LY294002, herbimycin
2
A, NS398, and PD98059 markedly inhibited the arecoline-induced PAR-1 expression
(p<0.05). Taken together, our findings demonstrated that PAR-1 expression is
significantly upregulated in areca quid chewing associated-OSF. In addition,
arecoline-induced PAR-1 expression was downregulated by NAC, LY294002,
herbimycin A, NS398, and PD98059.
