REGULATION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 MESSENGER-RNA ACCUMULATION BY BASIC FIBROBLAST-GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN CULTURED RAT ASTROCYTES

The effects of transforming growth factor-pi (TGF-beta 1) and basic fi broblast growth factor (bFGF) were examined on the accumulation of pla sminogen activator inhibitor-1 (PAI-1) mRNA in astrocytes in vitro, Bo th cytokines stimulated PAI-I mRNA expression transiently with a maxim al fivefold (bFGF) and 30-fold (TGF-beta 1) at 4 h, decreasing to basa l levels within 32 h, EC50 values were 1.4 nM for bFGF and 6.7 pM for TGF-beta 1 on PAI-I mRNA accumulation. A twofold increase in content o f tPA mRNA was observed with bFGF but not with TGF-beta 1. The action of TGF-beta 1 on PAI-I mRNA was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. In contrast, cycloheximi de potentiated the action of bFGF. Nuclear run-on assays showed that b FGF, but not TGF-beta 1, stimulated astrocytic PAI-1 gene transcriptio n. Thus, TGF-beta 1 predominantly uses posttranscriptional mechanisms to raise the level of PAI-1 mRNA in astrocytes, whereas bFGF acts at b oth the transcriptional and posttranscriptional levels. The data revea l differences in the mechanisms underlying the regulation of PAI-I mRN A levels by TGF-beta 1 in astrocytes compared with other cells. The ac tion of TGF-beta 1 and bFGF on the plasminogen activator system in ast rocytes might be involved in the cellular events accompanying glial ac tivation following injury of the CNS.