Type-I plasminogen activator inhibitor (PAI-1) is the primary inhibitor of both tissue- and urokinase-type plasminogen activators (t-PA, u-PA) and is thus a primary regulator of plasminogen activation and possibly of extracellular proteolysis. In anchorage-dependent cells, the PAI-1 gene was regulated by cell adhesion. PAI-1 gene expression was induced more evidently in cells adhered to the culture plate than in nonadherent cells. In this study, we investigated the signal pathway of the PAI-1 gene expression regulated by cell adhesion. We found the induction of both PAI-1 mRNA and protein, when cells adhered to culture dish, was inhibited by the PI-3 kinase specific inhibitors (Ly294002 and wortmannin). The cells seeded on collagen-1 coated plate with low serum further demonstrated that the PAI-1 gene expression was prolonged by the cell adhesion. The above-mentioned PI-3 kinase specific inhibitors also blocked the PAI-1 maintenance when cell adhered to collagen-1 coated plate. In addition, we found that both PI-3 kinase and its downstream molecule, Akt, were activated more evidently in adherent cells than in nonadherent cells. Furthermore, we transfected antisense oligodeoxynucleotides of Akt (AS-ODN-Akt) into cells to block the expression of Akt and found that the induction of PAI-1 mRNA was also inhibited. Hence, we conclude that the induction of PAI-1 gene expression is cell adhesion dependent and is through PI-3 kinase and Akt activation.
ASJC Scopus subject areas
- Cell Biology
- Clinical Biochemistry
Chang, H., Shyu, K-G., Lin, S., Wang, B. W., Liu, Y. C., & Lee, C. C. (2002). Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Communication and Adhesion, 9(5-6), 239-247. https://doi.org/10.1080/15419060216303