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• W2104602575 abstract "Objective: Aberrant regulation of the synthesis and degradation of the extracellular matrix (ECM) is associated with the pathophysiology of vascular disease. Plasminogen activator inhibitor-1 (PAI-1) plays a crucial role in regulating the quantity and composition of ECM. However, regulatory mechanisms underlying the expression of the PAI-1 gene remain unclear. We examined the effects of all-trans-retinoic acid (atRA), either alone or in combination with mitogenic growth factor, basic fibroblast growth factor (bFGF), on the PAI-1 expression in cultured vascular smooth muscle cells (SMCs). Methods: Cultures of the rabbit vascular smooth muscle cell line C2/2 were used to study the effects of atRA and bFGF separately or together. Results: Treatment of vascular SMCs with atRA in combination with bFGF resulted in an additional increase in PAI-1 expression both at the mRNA and protein levels. In contrast, tissue-type plasminogen activator, urokinase-type plasminogen activator and tissue factor mRNA levels were only minimally affected. The all-trans-RA- and bFGF-mediated increases in PAI-1 mRNA levels were markedly attenuated by the tyrosine kinase inhibitor genistein, but not by MEK1 or p38MAP kinase inhibitors. The rate of decrease in PAI-1 mRNA levels after actinomycin D treatment was not affected by atRA and bFGF. Transient transfection of the PAI-1 promoter-luciferase reporter gene, which contains 967 bp of the 5′-flanking region of the human PAI-1 gene, revealed that atRA and bFGF additionally increased transcription from this promoter. Progressive 5′-deletion revealed that the promoter region required for such an effect lies between −967 and −260, which contains no canonical sequence for the RA-response element. In agreement with the role of PAI-1 in the inhibition of fibrinolytic activity which stimulates ECM degradation, cell migration was inhibited by treatment with atRA and bFGF. Conclusions: These results indicate that atRA and bFGF can function in a combined fashion and induce PAI-1 synthesis in vascular SMCs, and suggest a role for these two compounds in regulating SMC migration." @default.
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• W2104602575 date "2001-07-01" @default.
• W2104602575 modified "2023-10-11" @default.
• W2104602575 title "Combined effect of retinoic acid and basic FGF on PAI-1 gene expression in vascular smooth muscle cells" @default.
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• W2104602575 doi "https://doi.org/10.1016/s0008-6363(01)00274-7" @default.
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