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- W2023196875 abstract "Upregulation of plasminogen activator inhibitor type 1 (PAI-1) expression is a critical mechanism through which transforming growth factor-beta1 (TGF-beta1) accelerates intimal growth. The aim of this study was to identify signaling pathways through which TGF-beta1 upregulates PAI-1 expression in endothelial cells (EC) and test interventions for blocking these pathways. We transduced cultured bovine EC with an adenoviral vector containing the PAI-1 promoter fused to a beta-galactosidase reporter gene. We used these cells, along with vectors expressing potential modifiers of TGF-beta1 signaling and pharmacologic antagonists of mitogen-activated protein kinase (MAPK) pathways to identify key mediators of basal and TGF-beta1-regulated PAI-1 expression. Basal activity of the PAI-1 promoter was directly correlated with Ras activation and was blocked by a dominant negative (DN) type I TGF-beta receptor. TGF-beta1-stimulated activity of the PAI-1 promoter did not require Ras activation, and was lessened or eliminated by expression of either DN type I or type II TGF-beta receptors and by inhibition of either of two MAPKs: MEK and p38. Our results suggest unanticipated pathways of TGF-beta1 signaling in EC and point to new strategies to limit TGF-beta1-induced vascular disease." @default.
- W2023196875 created "2016-06-24" @default.
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- W2023196875 creator A5041921017 @default.
- W2023196875 creator A5062478846 @default.
- W2023196875 date "2006-05-01" @default.
- W2023196875 modified "2023-09-23" @default.
- W2023196875 title "Identification of intracellular pathways through which TGF-β1 upregulates PAI-1 expression in endothelial cells" @default.
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- W2023196875 doi "https://doi.org/10.1016/j.atherosclerosis.2005.07.026" @default.
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