The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway

Hang Chang, Kou-Gi Shyu, Shankung Lin, Shiow Chwen Tsai, Bao Wei Wang, Ya Chen Liu, Yu Ling Sung, Chun Chung Lee

研究成果: 雜誌貢獻文章

12 引文 斯高帕斯(Scopus)

摘要

The type-I plasminogen activator inhibitor (PAI-1), the primary inhibitor of both tissue-type and urokinase-type plasminogen activators (t-PA, u-PA), is the primary regulator of plasminogen activation and possibly of extracellular proteolysis. In anchorage-dependent cells, the PAI-1 gene is regulated by cell adhesion. PAI-1 gene expression is induced more evidently in cells that adhered to the culture plate than in those that did not adhere. In this study, we further demonstrate that the PAI-1 gene expression associated with cell adhesion is elicited through the activation of MEK and p42/p44 mitogen-activated protein (MAP) kinase (MAPK; ERK) signal pathways. We found that the MEK inhibitors, PD98059 and U0126, inhibited the induction of PAI-1 gene and protein expression during cell adhesion, PD98059 also inhibited the adhesion of cells to the culture plate, and cell adhesion elicited the kinase activities of MEK and ERK. In addition, we illustrate that two transcription response elements, the serum response element (SRE) and the hypoxia response element (HRE), which exist in the PAI-1 promoter, might be correlated with PAI-1 gene expression during cell adhesion. We discovered that the binding ability of nucleoproteins to both SRE and HRE was enhanced by cell adhesion and was dependent on MEK. Based on these results, we suggest that both MEK and ERK are involved in the induction of PAI-1 gene expression during cell adhesion. Furthermore, the subsequent downstream molecules, Elk-1 and HIF-1, may also participate.
原文英語
頁(從 - 到)738-745
頁數8
期刊Journal of Biomedical Science
10
發行號6 II
DOIs
出版狀態已發佈 - 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

指紋 深入研究「The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway」主題。共同形成了獨特的指紋。

  • 引用此

    Chang, H., Shyu, K-G., Lin, S., Tsai, S. C., Wang, B. W., Liu, Y. C., Sung, Y. L., & Lee, C. C. (2003). The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway. Journal of Biomedical Science, 10(6 II), 738-745. https://doi.org/10.1159/000073961