抄録
Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of tissue-type and urokinase-type plasminogen activators (tPA, uPA), which convert plasminogen to plasmin. As plasmin plays a vital role in the regulation of intra- and extra-vascular fibrinolysis, the precise regulation of plasmin formation could provide a critical element of control in various processes such as fibrinolysis, tissue remodeling, inflammation and fibrous formation. We previously reported that prostaglandin I2 (PGI2) enhanced the expression of uPA in cultured human fibroblasts. In the present study, we examined the effect of PGI2 on PAI-1 expression by TIG 3-20 fibroblast cells. Northern analyses revealed that beraprost sodium, a stable PGI2 analog, inhibited PAI-1 mRNA expression induced by fetal calf serum in dose- and time-dependent manners. This inhibition by PGI2 was abolished in the presence of DRB, an inhibitor of transcription, suggesting that transcriptional mechanism was involved in the PAI-1 regulation. Cycloheximide, an inhibitor of translation, did not affect the inhibition of PGI2, suggesting that de novo protein synthesis was not required for the regulation. PGI2 also inhibited the PAI-1 mRNA expression induced by cytokines such as interleukin-1β, transforming growth factor-β and tumor necrosis factor-α. Although the precise mechanism of the inhibition by PGI2 has not been resolved in this study, it is likely that PGI2 can modulate the fibrinolytic activity of the cells through the inhibition of PAI-1 expression. [Jpn J Physiol 54 Suppl:S114 (2004)]
