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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Da Silva, Rita Graça Baker, Marianne Reynolds, Andrew R. Tavora, Bernardo Reynolds, Louise E. Marshall, John F. Hodivala-dilke, Kairbaan M. Robinson, Stephen D. Kostourou, Vassiliki |
| Description | Author Affiliation: Robinson SD ( Adhesion and Angiogenesis Laboratory, Tumour Biology Centre, Institute of Cancer, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom.) |
| Abstract | Both vascular endothelial growth factor receptors (VEGFR) and integrins are major regulators of VEGF-induced angiogenesis. Previous work has shown that beta3 integrin can regulate negatively VEGFR2 expression. Here we show that beta3 integrin can regulate negatively VEGF-mediated angiogenesis by limiting the interaction of the co-receptor NRP1 (neuropilin-1) with VEGFR2. In the presence of alphav beta3 integrin, NRP1 contributed minimally to VEGF-induced angiogenic processes in vivo, ex vivo, and in vitro. Conversely, when beta3 integrin expression is absent or low or its function is blocked with RGD-mimetic inhibitors, VEGF-mediated responses became NRP1-dependent. Indeed, combined inhibition of beta3 integrin and NRP1 decreased VEGF-mediated angiogenic responses further than individual inhibition of these receptors. We also show that alphav beta3 integrin can associate with NRP1 in a VEGF-dependent fashion. Our data suggest that beta3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 49 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-12-04 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Integrin AlphaVbeta3 Metabolism Neovascularization, Pathologic Neuropilin-1 Vascular Endothelial Growth Factor A Animals Aorta Cytology Endothelial Cells Mice Microcirculation Molecular Sequence Data Signal Transduction Vascular Endothelial Growth Factor Receptor-2 Wound Healing Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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