The upregulation of type I plasminogen activator inhibitor in oral submucous fibrosis.
Type I plasminogen activator inhibitor (PAI-1) is a 50 kDa glycoprotein belonging to the serine protease superfamily. PAI-1 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare PAI-1 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induced PAI-1 expression. Twenty-five OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. The activity of PAI-1 from cells cultured from OSF and normal buccal mucosa were assayed using reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blots. PAI-1 expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. In addition, OSF exhibited higher PAI-1 expression than normal buccal mucosa fibroblast (BMF) both in mRNA and protein levels. To verify whether arecoline, a major areca nut alkaloid, could affect PAI-1 expression by human BMFs, RT-PCR and Western blots were used. The results demonstrated highly elevated PAI-1 mRNA and protein expression in normal human BMFs stimulated by arecoline. Taken together, these results suggest that PAI-1 expression is significantly upregulated in OSF tissues from areca quid chewers, and arecoline may be responsible for the enhanced PAI-1 expression in vivo.
Yang
Shun-Fa
SF
Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan.
Hsieh
Yih-Shou
YS
Tsai
Chung-Hung
CH
Chou
Ming-Yung
MY
Chang
Yu-Chao
YC
D001114:Areca; D001115:Arecoline / Q000009:adverse effects*; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D002478:Cells, Cultured; D002610:Cheek; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009914:Oral Submucous Fibrosis / Q000139:chemically induced* / Q000378:metabolism; D010276:Parasympatholytics / Q000009:adverse effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D010276:Parasympatholytics; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D001115:Arecoline