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

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Larrivée B,Freitas C,Trombe M,Lv X,Delafarge B,Yuan L,Bouvrée K,Bréant C,Del Toro R,Bréchot N,Germain S,Bono F,Dol F,Claes F,Fischer C,Autiero M,Thomas JL,Carmeliet P,Tessier-Lavigne M,Eichmann A

doi

10.1101/gad.437807

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

2433-47

issue

19

eissn

0890-9369

issn

1549-5477

pii

21/19/2433

journal_volume

21

pub_type

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