| Autor: |
Erine H. Budi, Ons Mamai, Steven Hoffman, Rosemary J. Akhurst, Rik Derynck |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
iScience, Vol 11, Iss , Pp 474-491 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2018.12.038 |
| Popis: |
Summary: Angiogenesis, the development of new blood vessels, is a key process in disease. We reported that insulin promotes translocation of transforming growth factor β (TGF-β) receptors to the plasma membrane of epithelial and fibroblast cells, thus enhancing TGF-β responsiveness. Since insulin promotes angiogenesis, we addressed whether increased autocrine TGF-β signaling participates in endothelial cell responses to insulin. We show that insulin enhances TGF-β responsiveness and autocrine TGF-β signaling in primary human endothelial cells, by inducing a rapid increase in cell surface TGF-β receptor levels. Autocrine TGF-β/Smad signaling contributed substantially to insulin-induced gene expression associated with angiogenesis, including TGF-β target genes encoding angiogenic mediators; was essential for endothelial cell migration; and participated in endothelial cell invasion and network formation. Blocking TGF-β signaling impaired insulin-induced microvessel outgrowth from neonatal aortic rings and modified insulin-stimulated blood vessel formation in zebrafish. We conclude that enhanced autocrine TGF-β signaling is integral to endothelial cell and angiogenic responses to insulin. : Molecular Biology; Molecular Mechanism of Behavior; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Molecular Biology, Molecular Mechanism of Behavior, Cell Biology, Functional Aspects of Cell Biology |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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