REGULATION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 MESSENGER-RNA ACCUMULATION BY BASIC FIBROBLAST-GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN CULTURED RAT ASTROCYTES
Ja. Treichel et al., REGULATION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 MESSENGER-RNA ACCUMULATION BY BASIC FIBROBLAST-GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN CULTURED RAT ASTROCYTES, Journal of neurochemistry, 71(5), 1998, pp. 1944-1952
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.