PROSTAGLANDIN I-2 ANALOG ENHANCES THE EXPRESSION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND WOUND-HEALING IN CULTURED HUMAN FIBROBLAST

This study examines the effects of prostaglandin I-2 (PGI(2)) on uroki nase-type plasminogen activator (uPA) production and wound healing by human fibroblasts. Employing fibrin autography, it was found that bera prost sodium, a stable PGI2 analog, enhanced the fibrinolytic activity in media conditioned by human fibroblasts, TIG-3-20 cells. Fibrin zym ography, 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-I plasminogen activator inhibitor. While cyclohexi mide and 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor, suppr essed the effect of PGI2, dibutyryl cyclic AMP increased the fibrinoly tic activity and uPA mRNA. These findings indicate that PGI2 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 PGI2 itself did not affect cellular proliferation, it promoted in vitro repopulation of the denuded area in a wounded monolayer. These observations suggest that PGI2 can stimulate wound healing through the enhanced production of uPA. (C) 1998 Elsevier Science B.V.