Increased plasminogen activator inhibitor-1/tissue type plasminogen activator ratio in oral submucous fibrosis.
OBJECTIVE
Plasminogen activators and their inhibitors are thought to be key participants in the balance of proteolytic and antiproteolytic activities that regulate extracellular matrix (ECM) turnover. However, little is known about the expression of plasminogen/plasmin system at the site of oral submucous fibrosis (OSF).


METHODS
We compared the activities of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) between fibroblasts derived from normal buccal mucosa and OSF by using an enzyme-linked immunosorbent assay. Furthermore, arecoline, a major areca nut alkaloid, was challenged with normal buccal mucosal fibroblasts (BMFs) to elucidate whether the activities of t-PA and PAI-1 could be affected by arecoline.


RESULTS
Both t-PA and PAI-1 were found to be increased in OSF than in BMFs (P < 0.01). In addition, there was a statistically significant difference in PAI-1/t-PA ratio between OSF and BMF (P < 0.01). The addition of arecoline upregulated not only PAI-1, but also t-PA in BMFs (P < 0.05). In addition, the ratio between PAI-1 and t-PA was found to be significantly increased by a linear regression assay (P < 0.01).


CONCLUSIONS
These results suggest that OSF caused by areca quid chewing may be the result of an imbalance in the plasminogen/plasmin system, the net result of which is increased deposition of ECM.
Yang
S-F
SF
Institute of Medicine, Chung Shan Medical University, 110 Section 1 Chien-Kuo N. Road, Taichung, Taiwan.
Hsieh
Y-S
YS
Tsai
C-H
CH
Chen
Y-J
YJ
Chang
Y-C
YC
D001115:Arecoline / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000032:analysis* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism; D009914:Oral Submucous Fibrosis / Q000378:metabolism* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000032:analysis* / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000032:analysis* / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D018679:Cholinergic Agonists; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D001115:Arecoline; D010959:Tissue Plasminogen Activator