| First Author | Tian H | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 19 | Pages | 3885-900 |
| PubMed ID | 22940691 | Mgi Jnum | J:190018 |
| Mgi Id | MGI:5447854 | Doi | 10.1038/emboj.2012.246 |
| Citation | Tian H, et al. (2012) Endoglin mediates fibronectin/alpha5beta1 integrin and TGF-beta pathway crosstalk in endothelial cells. EMBO J 31(19):3885-900 |
| abstractText | Both the transforming growth factor beta (TGF-beta) and integrin signalling pathways have well-established roles in angiogenesis. However, how these pathways integrate to regulate angiogenesis is unknown. Here, we show that the extracellular matrix component, fibronectin, and its cellular receptor, alpha5beta1 integrin, specifically increase TGF-beta1- and BMP-9-induced Smad1/5/8 phosphorylation via the TGF-beta superfamily receptors endoglin and activin-like kinase-1 (ALK1). Fibronectin and alpha5beta1 integrin increase Smad1/5/8 signalling by promoting endoglin/ALK1 cell surface complex formation. In a reciprocal manner, TGF-beta1 activates alpha5beta1 integrin and downstream signalling to focal adhesion kinase (FAK) in an endoglin-dependent manner. alpha5beta1 integrin and endoglin form a complex on the cell surface and co-internalize, with their internalization regulating alpha5beta1 integrin activation and signalling. Functionally, endoglin-mediated fibronectin/alpha5beta1 integrin and TGF-beta pathway crosstalk alter the responses of endothelial cells to TGF-beta1, switching TGF-beta1 from a promoter to a suppressor of migration, inhibiting TGF-beta1-mediated apoptosis to promote capillary stability, and partially mediating developmental angiogenesis in vivo. These studies provide a novel mechanism for the regulation of TGF-beta superfamily signalling and endothelial function through crosstalk with integrin signalling pathways. |
