Details

Autor(en) / Beteiligte

• Budi, Erine H.
• Mamai, Ons
• Hoffman, Steven
• Akhurst, Rosemary J.
• Derynck, Rik

Titel

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

Ist Teil von

• iScience, 2019-01, Vol.11, p.474-491

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •Insulin promotes enhanced autocrine TGF-β responsiveness in endothelial cells•Autocrine TGF-β signaling contributes to insulin-induced angiogenesis gene expression•Insulin-induced endothelial migration and sprouting require autocrine TGF-β signaling•Enhanced autocrine TGF-β signaling is integral to angiogenic responses to insulin Molecular Biology; Molecular Mechanism of Behavior; Cell Biology; Functional Aspects of Cell Biology