Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts.

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Abstract
We have studied the mechanism of a transforming growth factor‐beta (TGF‐beta)‐stimulated production of type‐1 plasminogen activator inhibitor (PAI‐1) in WI‐38 human lung fibroblasts. TGF‐beta causes an early increase in the PAI‐1 mRNA level which reaches a maximal 50‐fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI‐1 mRNA. Quantitative studies of the effect of TGF‐beta on PAI‐1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI‐1 mRNA. The results suggest a primary effect of TGF‐beta on PAI‐1 gene transcription, and also suggest the possibility that the transcription of this gene in non‐induced cells may be suppressed by a short‐lived negatively regulating protein. Urokinase‐type (u‐PA) and tissue‐type (t‐PA) plasminogen activators are decreased in the culture media of TGF‐beta‐treated cells concomitantly with the increase in PAI‐1 accumulation. These findings show that a primary and important biological effect of TGF‐beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF‐beta action at the genetic level.

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