Objective: Oral submucous fibrosis (OSF) is a pre-malignant fibrotic lesion of the mouth in areca quid chewers. It is probably a consequence of disturbances in the hemeostatic equilibrium between synthesis and degradation of extracellular matrix molecules (ECM). Plasminogen activators and their inhibitors are thought to be key participates in the balance of proteolytic and antiproteolytic activities that regulates ECM turnover. In this study, we examined the activity of tissue type plasminogen activator (t-PA) and type I plasminogen activator inhibitor (PAI-1) from cultured cells from OSF and normal buccal mucosa. Methods: Fibroblast strains from 25 OSF and 10 normal buccal mucosa were used to compare t-PA and PAI-1 activity by enzyme-linked immunosorbent assay (ELISA). Cells were incubation for 24 h, conditioned media were collected and subsequently assayed. Furthermore, primary normal buccal mucosa fibroblasts (BMF) were challenged with arecoline, to explore the potential mechanism for areca quid associated OSF. Results: OSF exhibited higher t-PA and PAI-1 expression than BMF (P<0.05). The amounts of t-PA and PAI-1 were about 2.7 and 3.2 fold as compared with BMF, respectively. In addition, the PAI-1/tPA ratio was significantly higher in OSF than BMF (P<0.05). In addition, arecoline was found to increase t-PA and PAI-1 secretion in a dose-dependent manner in BMF cultures (P<0.05). Moreover, the PAI/t-PA ratio in arecoline treated BMF was also >1. Conclusions: Our study demonstrates that both t-PA and PAI-1 activity were upregulated in OSF as compared with BMF. OSF caused by areca quid chewing may be the result of an imbalance between enhanced ECM synthesis and diminished breakdown of connective tissue proteins, the net results of which is increased deposition of ECM. This study was supported by NSC 92-2314-B-040-016.

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