Prostaglandin I 2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast

Abstract

This study examines the effects of prostaglandin I 2 (PGI 2) on urokinase-type plasminogen activator (uPA) production and wound 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.