Prostaglandin I_2 analog enhances the expression of urokinase-type plasminogena ctivator and wound healing in cultured human fibroblast

摘要

This study examines the effects of prostaglandin I_2 (PGI_2) on urokinase-type plasminogen activator (uPA) production and would healing by human fibroblasts. Employing fibrin autography, it was found that beraprost sodium, a stable PGI_2 analog, enhanced the fibrinolytic activity in media conditioned by human fibroblasts, TIG-3-20 cells. Fibrin zymography, ELISA, and Northern blot analysis confirmed that the enhanced activity was caused by an increase in uPA synthesis and secretion and a decrease in type-1 plasminogen activator inhibitor. While cycloheximide and 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor, suppressed the effect of PGI_2, dibutyryl cyclic AMP increased the fibrinolytic activity and uPA mRNA. These findings indicate that PGI_2 promotes uPA production in TIG-3-20 cells via direct stimulation of the cyclic AMP intracellular pathway. A similar effect was observed in two other fibroblast cell lines, TIG-7-20 and TIG-7-30 . Although PGI_2 itself did not affect cellular proliferation, it promoted in vitro repopulation of the denuded area in a wounded monolayer. These observations suggest that PGI_2 can stimulate wound healing through the enhanced production of uPA.