| First Author | Liu Z | Year | 2009 |
| Journal | J Cell Sci | Volume | 122 |
| Issue | Pt 18 | Pages | 3294-302 |
| PubMed ID | 19706683 | Mgi Jnum | J:153082 |
| Mgi Id | MGI:4360840 | Doi | 10.1242/jcs.048942 |
| Citation | Liu Z, et al. (2009) VEGF and inhibitors of TGFbeta type-I receptor kinase synergistically promote blood-vessel formation by inducing alpha5-integrin expression. J Cell Sci 122(Pt 18):3294-302 |
| abstractText | Vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGFbeta) are potent regulators of angiogenesis. How VEGF and TGFbeta signaling pathways crosstalk is not well understood. Therefore, we analyzed the effects of the TGFbeta type-I-receptor inhibitors (SB-431542 and LY-2157299) and VEGF on endothelial cell (EC) function and angiogenesis. We show that SB-431542 dramatically enhances VEGF-induced formation of EC sheets from fetal mouse metatarsals. Sub-optimal doses of VEGF and SB-431542 synergistically induced EC migration and sprouting of EC spheroids, whereas overexpression of a constitutively active form of TGFbeta type-I receptor had opposite effects. Using quantitative PCR, we demonstrated that VEGF and SB-431542 synergistically upregulated the mRNA expression of genes involved in angiogenesis, including the integrins alpha5 and beta3. Specific downregulation of alpha5-integrin expression or functional blocking of alpha5 integrin with a specific neutralizing antibody inhibited the cooperative effect of VEGF and SB-431542 on EC sprouting. In vivo, LY-2157299 induced angiogenesis and enhanced VEGF- and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin-neutralizing antibody to the Matrigel selectively inhibited this enhanced response. Thus, induction of alpha5-integrin expression is a key determinant by which inhibitors of TGFbeta type-I receptor kinase and VEGF synergistically promote angiogenesis. |
