Transforming growth factor-beta induces endothelin-1 expression through activation of the Smad signaling pathway
| Autor: | Fernando Rodríguez-Pascual, Santiago Lamas, Mariano Redondo-Horcajo, Francisco Manuel Reimunde |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Transcriptional Activation
Time Factors GDF2 SMAD Transfection GDF1 Mothers against decapentaplegic homolog 2 Transforming Growth Factor beta1 Mothers against decapentaplegic homolog 3 SMAD binding Animals Humans Smad3 Protein Phosphorylation Promoter Regions Genetic Cells Cultured Pharmacology Endothelin-1 Chemistry Endothelial Cells Recombinant Proteins Cell biology Up-Regulation Transcription Factor AP-1 Transforming growth factor beta 3 Mutation Cattle Cardiology and Cardiovascular Medicine Transforming growth factor Signal Transduction |
| Zdroj: | Journal of cardiovascular pharmacology. 44 |
| ISSN: | 1533-4023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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