Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability.

Nature Medicine
Christopher A JonesDean Y Li

Abstract

The angiogenic sprout has been compared to the growing axon, and indeed, many proteins direct pathfinding by both structures. The Roundabout (Robo) proteins are guidance receptors with well-established functions in the nervous system; however, their role in the mammalian vasculature remains ill defined. Here we show that an endothelial-specific Robo, Robo4, maintains vascular integrity. Activation of Robo4 by Slit2 inhibits vascular endothelial growth factor (VEGF)-165-induced migration, tube formation and permeability in vitro and VEGF-165-stimulated vascular leak in vivo by blocking Src family kinase activation. In mouse models of retinal and choroidal vascular disease, Slit2 inhibited angiogenesis and vascular leak, whereas deletion of Robo4 enhanced these pathologic processes. Our results define a previously unknown function for Robo receptors in stabilizing the vasculature and suggest that activating Robo4 may have broad therapeutic application in diseases characterized by excessive angiogenesis and/or vascular leak.

References

Jun 18, 2003·The Journal of Cell Biology·Holger GerhardtChrister Betsholtz
Aug 28, 2003·Developmental Biology·Kye Won ParkDean Y Li
Sep 19, 2003·Trends in Biochemical Sciences·Michael J CrossLena Claesson-Welsh
Oct 16, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Steven SuchtingRoy Bicknell
Jan 5, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shinong WangRaimund Hirschberg
May 17, 2005·Biochemical and Biophysical Research Communications·Pankaj SethVikas P Sukhatme
Jul 15, 2005·Nature·Peter Carmeliet, Marc Tessier-Lavigne
Aug 27, 2005·Investigative Ophthalmology & Visual Science·Raquel Lima e SilvaPeter A Campochiaro
Dec 13, 2005·Experimental Cell Research·Akiyoshi UemuraShin-Ichi Nishikawa
Feb 17, 2006·The Journal of Biological Chemistry·Sukhbir KaurRamani Ramchandran
Oct 6, 2006·The New England Journal of Medicine·Philip J RosenfeldUNKNOWN MARINA Study Group
Oct 6, 2006·The New England Journal of Medicine·David M BrownUNKNOWN ANCHOR Study Group
Sep 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Cecile MorlotAndrew A McCarthy

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Citations

Apr 6, 2011·Histochemistry and Cell Biology·Cai Feng DaiJing Zheng
Jan 28, 2009·Angiogenesis·Nyall R LondonDean Y Li
May 29, 2012·Current Diabetes Reports·Shuang WangElia J Duh
Oct 27, 2009·Nature Cell Biology·Christopher A JonesDean Y Li
Feb 18, 2011·Nature Reviews. Cancer·Patrick MehlenAlain Chédotal
Aug 24, 2011·Nature Reviews. Molecular Cell Biology·Shane P Herbert, Didier Y R Stainier
May 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Rebecca MarlowLindsay Hinck
Dec 20, 2008·Lymphatic Research and Biology·Michael R MancusoCalvin J Kuo
Nov 30, 2011·Cerebral Cortex·Wang ZhengXiao-bing Yuan
Jul 24, 2010·Molecular Human Reproduction·W C DuncanA W Horne
Jan 21, 2012·Biology of Reproduction·Wu-Xiang LiaoDong-Bao Chen
Jun 30, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kent S BolesGregory M Lanza
May 23, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Liya PiEdward W Scott
May 11, 2010·Cold Spring Harbor Perspectives in Biology·Ralf H Adams, Anne Eichmann
May 13, 2011·The Journal of Pharmacology and Experimental Therapeutics·Benjamin A NacevJun O Liu
Jan 8, 2009·Science Signaling·Jason E Fish, Deepak Srivastava
Apr 9, 2010·Science Translational Medicine·Nyall R LondonDean Y Li
Dec 24, 2010·Journal of Virology·Elena E GorbunovaErich R Mackow
Dec 8, 2010·Molecular and Cellular Biology·Charlene M DunawayDana M Brantley-Sieders
Jul 20, 2012·Advances in Virology·Irina GavrilovskayaErich Mackow
Jan 18, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Lan T H DangJason E Fish
Oct 16, 2010·Circulation Research·Eric M SmallEric N Olson
Apr 15, 2011·The Journal of Clinical Investigation·Aubrey C ChanDean Y Li
Aug 3, 2013·The Journal of Clinical Investigation·Jonathan WeltiPeter Carmeliet
Aug 7, 2012·Genes & Cancer·Safiyyah Ziyad, M Luisa Iruela-Arispe
Nov 5, 2008·BMC Cell Biology·Sukhbir KaurRamani Ramchandran
Oct 2, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoshiaki Okada
Jan 4, 2013·PloS One·Justin ByunFeng-Quan Zhou

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