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ZFIN ID: ZDB-PUB-150207-2
CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development
Tu, T., Zhang, C., Yan, H., Luo, Y., Kong, R., Wen, P., Ye, Z., Chen, J., Feng, J., Liu, F., Wu, J.Y., Yan, X.
Date: 2015
Source: Cell Research   25(3): 275-87 (Journal)
Registered Authors: Liu, Feng, Zhang, Chunxia
Keywords: none
MeSH Terms:
  • Animals
  • CD146 Antigen/genetics
  • CD146 Antigen/metabolism
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells/physiology
  • Humans
  • Mice
  • Mice, Transgenic
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology*
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Cell Surface/genetics
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Vascular Endothelial Growth Factor Receptor-2/metabolism
  • Zebrafish
PubMed: 25656845 Full text @ Cell Res.
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ABSTRACT
Angiogenesis, a process that newly-formed blood vessels sprout from pre-existing ones, is vital for vertebrate development and adult homeostasis. Previous studies have demonstrated that the neuronal guidance molecule netrin-1 participates in angiogenesis and morphogenesis of the vascular system. Netrin-1 exhibits dual activities in angiogenesis: either promoting or inhibiting angiogenesis. The anti-angiogenic activity of netrin-1 is mediated by UNC5B receptor. However, how netrin-1 promotes angiogenesis remained unclear. Here we report that CD146, an endothelial transmembrane protein of the immunoglobulin superfamily, is a receptor for netrin-1. Netrin-1 binds to CD146 with high affinity, inducing endothelial cell activation and downstream signaling in a CD146-dependent manner. Conditional knockout of the cd146 gene in the murine endothelium or disruption of netrin-CD146 interaction by a specific anti-CD146 antibody blocks or reduces netrin-1-induced angiogenesis. In zebrafish embryos, downregulating either netrin-1a or CD146 results in vascular defects with striking similarity. Moreover, knocking down CD146 blocks ectopic vascular sprouting induced by netrin-1 overexpression. Together, our data uncover CD146 as a previously unknown receptor for netrin-1 and also reveal a functional ligand for CD146 in angiogenesis, demonstrating the involvement of netrin-CD146 signaling in angiogenesis during vertebrate development.Cell Research advance online publication 6 February 2015; doi:10.1038/cr.2015.15.
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