Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast.
This study examines the effects of prostaglandin I2 (PGI2) on urokinase-type plasminogen activator (uPA) production and wound healing by human fibroblasts. Employing fibrin autography, it was found that beraprost sodium, a stable PGI2 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 PGI2, dibutyryl cyclic AMP increased the fibrinolytic 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.
Hatane
T
T
Department of Physiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-16, Japan. thatane@post1.miyazaki-med.ac.jp
Yoshida
E
E
Kawano
J
J
Sugiki
M
M
Onitsuka
T
T
Maruyama
M
M
D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*
D012333:RNA, Messenger; C048081:beraprost; D011464:Epoprostenol; D014568:Urokinase-Type Plasminogen Activator