Netrins promote developmental and therapeutic angiogenesis |
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Authors: | Wilson Brent D Ii Masaaki Park Kye Won Suli Arminda Sorensen Lise K Larrieu-Lahargue Fréderic Urness Lisa D Suh Wonhee Asai Jun Kock Gerhardus A H Thorne Tina Silver Marcy Thomas Kirk R Chien Chi-Bin Losordo Douglas W Li Dean Y |
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Institution: | Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112, USA. |
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Abstract: | Axonal guidance and vascular patterning share several guidance cues, including proteins in the netrin family. We demonstrate that netrins stimulate proliferation, migration, and tube formation of human endothelial cells in vitro and that this stimulation is independent of known netrin receptors. Suppression of netrin1a messenger RNA in zebrafish inhibits vascular sprouting, implying a proangiogenic role for netrins during vertebrate development. We also show that netrins accelerate neovascularization in an in vivo model of ischemia and that they reverse neuropathy and vasculopathy in a diabetic murine model. We propose that the attractive vascular and neural guidance functions of netrins offer a unique therapeutic potential. |
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