ZFIN ID: ZDB-PUB-060703-18
Netrins Promote Developmental and Therapeutic Angiogenesis
Wilson, B.D., Ii, M., Park, K.W., Suli, A., Sorensen, L.K., Larrieu-Lahargue, F., Urness, L.D., Suh, W., Asai, J., Kock, G.A., Thorne, T., Silver, M., Thomas, K.R., Chien, C.B., Losordo, D.W., and Li, D.Y.
Date: 2006
Source: Science (New York, N.Y.)   313(5787): 640-644 (Journal)
Registered Authors: Chien, Chi-Bin, Suli, Arminda
Keywords: none
MeSH Terms:
  • Angiogenesis Inducing Agents
  • Animals
  • Cell Line
  • Cell Movement
  • Chemotaxis
  • DNA, Complementary
  • Diabetic Angiopathies/therapy
  • Diabetic Neuropathies/therapy
  • Embryo, Nonmammalian
  • Endothelial Cells/physiology*
  • Endothelium, Vascular/cytology
  • Genetic Therapy
  • Humans
  • Ischemia/drug therapy
  • Mice
  • Muscle, Skeletal/blood supply
  • Neovascularization, Physiologic*
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/pharmacology
  • Nerve Growth Factors/physiology*
  • Neural Conduction
  • Receptors, Cell Surface/physiology
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/pharmacology
  • Tumor Suppressor Proteins/physiology*
  • Vascular Endothelial Growth Factor A/therapeutic use
  • Zebrafish
PubMed: 16809490 Full text @ Science
Axonal guidance and vascular patterning share several guidance cues, including proteins of the netrin family. We demonstrate that netrins stimulate the proliferation, migration and tube formation of human endothelial cells in vitro, and that this stimulation is independent of known netrin receptors. Knockdown of netrin1a mRNA in zebrafish inhibits vascular sprouting, implying a pro-angiogenic 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.