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

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH08-05-0294
Issue:2008: 100/6 (Dec) pp. 955-1217
Pages:1007-1013

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

Yoshikuni Nagamine

Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland

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

DOI

http://dx.doi.org/10.1160/TH08-05-0294

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