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- Title
Activation of the UNC5B receptor by Netrin-1 inhibits neovascularization.
- Authors
Larrivée, Bruno; Freitas, Catarina; Trombe, Marc; Xiang Lv; DeLafarge, Benjamin; Li Yuan; Bouvrée, Karine; Breant, Christiane; Bono, Francoise; Autiero, Monica; Claes, Filip; Carmeliet, Peter; Tessier-Lavigne, Marc; Eichmann, Anne
- Abstract
Netrins are secreted molecules with roles in axonal growth and angiogenesis. Our previous work has implicated the Netrin receptor UNC5B in embryonic vascular patterning, but its function in postnatal vascular development and in pathological angiogenesis in the adult is unknown. We show that unc5b is expressed by sprouting capillaries during postnatal and tumor angiogenesis. Deletion of the unc5b gene leads to increased vessel branching in the postnatal mouse retina. Netrin-1 stimulation of UNCSB-expressing neovessels reduces sprouting angiogenesis in aortic ring, matrigel and tumor models. Expression of UNC5B full-length receptor triggers endothelial cell repulsion in response to Netrin-1 in vitro, whereas a truncated UNCSB lacking the intracellular signaling domain fails to induce repulsion. Collectively, these data show that UNC5B receptor activation inhibits neovascularization, thus identifying UNC5B as a potential anti-angiogenic target.
- Subjects
PROTEINS; NEOVASCULARIZATION; HEART tumors; CELLULAR signal transduction; LABORATORY mice
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA746
- ISSN
0892-6638
- Publication type
Article