Enhanced TGF-? Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells.

ABSTRACT: Angiogenesis, the development of new blood vessels, is a key process in disease. We reported that insulin promotes translocation of transforming growth factor ? (TGF-?) receptors to the plasma membrane of epithelial and fibroblast cells, thus enhancing TGF-? responsiveness. Since insulin promotes angiogenesis, we addressed whether increased autocrine TGF-? signaling participates in endothelial cell responses to insulin. We show that insulin enhances TGF-? responsiveness and autocrine TGF-? signaling in primary human endothelial cells, by inducing a rapid increase in cell surface TGF-? receptor levels. Autocrine TGF-?/Smad signaling contributed substantially to insulin-induced gene expression associated with angiogenesis, including TGF-? target genes encoding angiogenic mediators; was essential for endothelial cell migration; and participated in endothelial cell invasion and network formation. Blocking TGF-? 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-? signaling is integral to endothelial cell and angiogenic responses to insulin.

SUBMITTER: Budi EH 

PROVIDER: S-EPMC6348203 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature