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• W2134734822 endingPage "134" @default.
• W2134734822 startingPage "125" @default.
• W2134734822 abstract "Endothelin (ET)-1 is a potent vasoconstrictor that participates in cardiovascular diseases. Connective tissue growth factor (CTGF) is a novel fibrotic mediator that is overexpressed in human atherosclerotic lesions, myocardial infarction, and experimental models of hypertension. In vascular smooth muscle cells (VSMCs), CTGF regulates cell proliferation/apoptosis, migration, and extracellular matrix (ECM) accumulation. Our aim was to investigate whether ET-1 could regulate CTGF and to investigate the potential role of ET-1 in vascular fibrosis. In growth-arrested rat VSMCs, ET-1 upregulated CTGF mRNA expression, promoter activity, and protein production. The blockade of CTGF by a CTGF antisense oligonucleotide decreased FN and type I collagen expression in ET-1–treated cells, showing that CTGF participates in ET-1–induced ECM accumulation. The ET A , but not ET B , antagonist diminished ET-1–induced CTGF expression gene and production. Several intracellular signals elicited by ET-1, via ET A receptors, are involved in CTGF synthesis, including activation of RhoA/Rho-kinase and mitogen-activated protein kinase and production of reactive oxygen species. CTGF is a mediator of TGF-β– and angiotensin (Ang) II–induced fibrosis. In VSMCs, ET-1 did not upregulate TGF-β gene or protein. The presence of neutralizing transforming growth factor (TGF)-β antibody did not modify ET-1–induced CTGF production, showing a TGF-β–independent regulation. We have also found an interrelationship between Ang II and ET-1 because the ET A antagonist diminished CTGF upregulation caused by Ang II. Collectively, our results show that, in cultured VSMCs, ET-1, independently of TGF-β and through the activation of several intracellular signals via ET A receptors, regulates CTGF. This novel finding suggests that CTGF could be a mediator of the profibrotic effects of ET-1 in vascular diseases." @default.
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• W2134734822 date "2005-07-22" @default.
• W2134734822 modified "2023-10-18" @default.
• W2134734822 title "Endothelin-1, via ET _A Receptor and Independently of Transforming Growth Factor-β, Increases the Connective Tissue Growth Factor in Vascular Smooth Muscle Cells" @default.
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• W2134734822 doi "https://doi.org/10.1161/01.res.0000174614.74469.83" @default.
• W2134734822 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15976312" @default.
• W2134734822 hasPublicationYear "2005" @default.
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