Regulation of plasminogen activator inhibitor-1 mRNA accumulation by basic fibroblast growth factor and transforming growth factor-beta1 in cultured rat astrocytes.
The effects of transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) were examined on the accumulation of plasminogen activator inhibitor-1 (PAI-1) mRNA in astrocytes in vitro. Both cytokines stimulated PAI-1 mRNA expression transiently with a maximal fivefold (bFGF) and 30-fold (TGF-beta1) at 4 h, decreasing to basal levels within 32 h. EC50 values were 1.4 nM for bFGF and 6.7 pM for TGF-beta1 on PAI-1 mRNA accumulation. A twofold increase in content of tPA mRNA was observed with bFGF but not with TGF-beta1. The action of TGF-beta1 on PAI-1 mRNA was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. In contrast, cycloheximide potentiated the action of bFGF. Nuclear run-on assays showed that bFGF, but not TGF-beta1, stimulated astrocytic PAI-1 gene transcription. Thus, TGF-beta1 predominantly uses posttranscriptional mechanisms to raise the level of PAI-1 mRNA in astrocytes, whereas bFGF acts at both the transcriptional and posttranscriptional levels. The data reveal differences in the mechanisms underlying the regulation of PAI-1 mRNA levels by TGF-beta1 in astrocytes compared with other cells. The action of TGF-beta1 and bFGF on the plasminogen activator system in astrocytes might be involved in the cellular events accompanying glial activation following injury of the CNS.
Treichel
J A
JA
Department of Neuromorphology, Max Planck Institute of Neurobiology, Martinsried, Germany.
Reddington
M
M
Kreutzberg
G W
GW
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002452:Cell Count; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D019384:Nucleic Acid Synthesis Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D003609:Dactinomycin; D005576:Colforsin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate