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Publication : Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis.

First Author  Larrivée B Year  2007
Journal  Genes Dev Volume  21
Issue  19 Pages  2433-47
PubMed ID  17908930 Mgi Jnum  J:125488
Mgi Id  MGI:3758967 Doi  10.1101/gad.437807
Citation  Larrivee B, et al. (2007) Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes Dev 21(19):2433-47
abstractText  Netrins are secreted molecules with roles in axonal growth and angiogenesis. The Netrin receptor UNC5B is required during embryonic development for vascular patterning, suggesting that it may also contribute to postnatal and pathological angiogenesis. Here we show that unc5b is down-regulated in quiescent adult vasculature, but re-expressed during sprouting angiogenesis in matrigel and tumor implants. Stimulation of UNC5B-expressing neovessels with an agonist (Netrin-1) inhibits sprouting angiogenesis. Genetic loss of function of unc5b reduces Netrin-1-mediated angiogenesis inhibition. Expression of UNC5B full-length receptor also triggers endothelial cell repulsion in response to Netrin-1 in vitro, whereas a truncated UNC5B lacking the intracellular signaling domain fails to induce repulsion. These data show that UNC5B activation inhibits sprouting angiogenesis, thus identifying UNC5B as a potential anti-angiogenic target.
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