Transcriptional regulation of the plasminogen activator inhibitor type 1--with an emphasis on negative regulation.

ABSTRACT

By inhibiting plasminogen activators uPA and tPA, inducing uPA-uPAR internalization and interfering with the interaction between extracellular matrix protein vitronectin and alphavbeta3 integrin, plasminogen activator inhibitor type 1 (PAI-1) is active in the regulation of various biological processes involving extracellular proteolysis and tissue remodeling. PAI-1 is expressed in many cell types under the control of a variety of signals, depending on cell type. The most prominent and important of these signals are TGFbeta, hypoxia and insulin. Although the signaling pathways were largely elucidated, recent investigations have revealed more complicated aspects. The pathways interact at the level of both transcription factors and regulatory elements on the promoter. Furthermore, the engagement of negative factors in these pathways has been shown to be important, adding complexity and versatility to PAI-1 gene regulation.