Retinoids induce the PAI-1 gene expression through tyrosine kinase-dependent pathways in vascular smooth muscle cells

Journal of Cardiovascular Pharmacology
Atai WatanabeMasahiko Kurabayashi

Abstract

Retinoids exert their pleiotropic effects on several pathophysiologic processes, including neointima formation after experimental vascular injury. Plasminogen activator inhibitor-1 (PAI-1) has been proposed to play an inhibitory role in arterial neointima formation after injury. We examined whether retinoids regulate PAI-1 expression in cultured vascular smooth muscle cells (SMCs). Northern blot analysis showed that all-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) increased PAI-1 mRNA levels in a dose-dependent manner. These responses were completely inhibited by tyrosine kinase inhibitors. The half-life of PAI-1 was not affected by atRA, suggesting that induction of PAI-1 mRNA was mainly regulated at the transcriptional levels. Stable and transient transfection assays of the human PAI-1 promoter-luciferase constructs indicate that DNA sequence responsive to either ligand-stimulated or overexpressed retinoic acid receptor-alpha expression vector lies downstream of -363 relative to the transcription start site, where no putative retinoic acid response element is found. These results indicate that atRA and 9cRA increase PAI-1 gene transcription through pathways involving tyrosine kinases in SMCs. Because PAI-1 inhibi...Continue Reading

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Citations

Sep 3, 2013·British Journal of Pharmacology·A C RankinQ Xu
Aug 4, 2011·Biochimica Et Biophysica Acta·Eun-Jung RheeJorge Plutzky
Apr 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ovidiu MituIrina Iuliana Costache

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