Netrins promote developmental and therapeutic angiogenesis.
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.
Wilson
Brent D
BD
Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Ii
Masaaki
M
Park
Kye Won
KW
Suli
Arminda
A
Sorensen
Lise K
LK
Larrieu-Lahargue
Fréderic
F
Urness
Lisa D
LD
Suh
Wonhee
W
Asai
Jun
J
Kock
Gerhardus A H
GA
Thorne
Tina
T
Silver
Marcy
M
Thomas
Kirk R
KR
Chien
Chi-Bin
CB
Losordo
Douglas W
DW
Li
Dean Y
DY
D043925:Angiogenesis Inducing Agents; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D018076:DNA, Complementary; D003925:Diabetic Angiopathies / Q000628:therapy; D003929:Diabetic Neuropathies / Q000628:therapy; D004625:Embryo, Nonmammalian; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000188:drug therapy; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D009431:Neural Conduction; D011956:Receptors, Cell Surface / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use; D015027:Zebrafish
D043925:Angiogenesis Inducing Agents; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D000075385:Netrins; C416214:Ntn4 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D000075388:Netrin-1; C088894:netrin-2