Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast

Autor: Etsuo Yoshida, Masahiko Sugiki, Masugi Maruyama, Jiro Kawano, Toshihiko Hatane, Toshio Onitsuka
Rok vydání: 1998
Předmět:
Zdroj: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1403:189-198
ISSN: 0167-4889
DOI: 10.1016/s0167-4889(98)00041-x
Popis: 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.
Databáze: OpenAIRE
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