PUBLICATION
Enhanced TGF-β Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells
- Authors
- Budi, E.H., Mamai, O., Hoffman, S., Akhurst, R.J., Derynck, R.
- ID
- ZDB-PUB-190127-17
- Date
- 2019
- Source
- iScience 11: 474-491 (Journal)
- Registered Authors
- Budi, Erine
- Keywords
- Cell Biology, Functional Aspects of Cell Biology, Molecular Biology, Molecular Mechanism of Behavior
- MeSH Terms
- none
- PubMed
- 30684493 Full text @ iScience
Citation
Budi, E.H., Mamai, O., Hoffman, S., Akhurst, R.J., Derynck, R. (2019) Enhanced TGF-β Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells. iScience. 11:474-491.
Abstract
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.
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