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Thromb Haemost 2008; 100(06): 1007-1013
DOI: 10.1160/TH08-05-0294
Theme Issue Article
Schattauer GmbH

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

Yoshikuni Nagamine
1   Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland
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Publication History

Received: 08 May 2008

Accepted after minor revision: 18 July 2008

Publication Date:
23 November 2017 (online)

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Summary

By inhibiting plasminogen activators uPA and tPA, inducing uPAuPAR internalization and interfering with the interaction between extracellular matrix protein vitronectin and αvβ3 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 TGFβ, 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.

Keywords

Review - plasminogen activator - gene regulation - negative regulation
 

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