We have explored the effect of insulin on the modulation of mRNA and antigen levels of components of the fibrinolytic enzyme system in human hepatoma (Hep G2) and fibrosarcoma (HT-1080) cells. Treatment of Hep G2 cells with a physiological concentration of insulin provokes a 2-fold increase in plasminogen activator inhibitor (PAI)-1 antigen. A similar increase is observed for both the 3.2 and 2.3 kb transcripts of PAI-1 mRNA. Cycloheximide when added alone to cells preferentially suppresses constitutive expression of the 3.2 kb PAI-1 mRNA and blocks insulin-mediated induction of both 3.2 and 2.3kb PAI-1 mRNA. There was no detectable expression of urokinase (u-PA) or tissue-type plasminogen activator (t-PA) antigen or mRNA in these cells under constitutive conditions or after treatment with insulin. In HT-1080 cells, basal expression of PAI-1, t-PA and u-PA mRNA and antigen was not modulated by insulin treatment. The results from these experiments indicate firstly, that induction of PAI-1 by insulin requires on-going protein biosynthesis, and secondly, that the two species of PAI-1 mRNA have a different requirement for protein biosynthesis.
- Plasminogen activator inhibitor 1