| Literature DB >> 15838328 |
Fernando Rodríguez-Pascual1, Francisco Manuel Reimunde, Mariano Redondo-Horcajo, Santiago Lamas.
Abstract
Expression of the endothelin-1 gene is subject to complex regulation by different factors, among which transforming growth factor-beta is one of the most important. We have analyzed the mechanism by which transforming growth factor-beta increases endothelin-1 expression in vascular endothelial cells. Transcriptional activation of the endothelin-1 promoter accounted for the transforming growth factor-beta-induced increase in endothelin-1 mRNA levels. Two DNA elements within the promoter are responsible for this effect: a Smad binding element and a proximal activator protein-1 site. Mutation of both elements abolished transforming growth factor-beta responsiveness. Overexpression of the Smad3 isoform strongly potentiates transforming growth factor-beta- induced endothelin-1 promoter activity in a phosphorylation-dependent manner. These results demonstrate that transforming growth factor-beta induces endothelin-1 expression by a functional cooperation between Smads and activator protein-1 through activation of the Smad signaling pathway.Entities:
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Year: 2004 PMID： 15838328 DOI： 10.1097/01.fjc.0000166216.27544.22
Source DB: PubMed Journal: J Cardiovasc Pharmacol ISSN： 0160-2446 Impact factor: 3.105