The critical role of the interplays of EphrinB2/EphB4 and VEGF in the induction of angiogenesis

Mol Biol Rep. 2020 Jun;47(6):4681-4690. doi: 10.1007/s11033-020-05470-y. Epub 2020 Jun 2.

Abstract

The significant role of VEGF (vascular endothelial growth factor) as an angiogenesis inducer is well recognized. Besides VEGF, EphrinB2/EphB4 also plays essential roles in vascular development and postnatal angiogenesis. Compared with classical proangiogenic factors, not only does EphrinB2/EphB4 promote sprouting of new vessels, it is also involved in the vessel maturation. Given their involvement in many physiologic and pathological conditions, EphB4 and EphrinB2 are increasingly recognized as attractive therapeutic targets for angiogenesis-related diseases through modulating their expression and function. Previous works mainly focused on the individual role of VEGF and EphrinB2/EphB4 in angiogenesis, respectively, but the correlation between EphrinB2/EphB4 and VEGF in angiogenesis has not been fully disclosed. Here, we summarize the structure and bidirectional signaling of EphrinB2/EphB4, provide an overview on the relationship between EphrinB2/EphB4 signaling and VEGF pathway in angiogenesis and highlight the associated potential usefulness in anti-angiogenetic therapy.

Keywords: Angiogenesis; EphrinB2/EphB4; VEGF.

Publication types

  • Review

MeSH terms

  • Animals
  • Cells, Cultured
  • Endothelial Cells / metabolism
  • Ephrin-B2 / metabolism*
  • Ephrin-B2 / physiology
  • Humans
  • Morphogenesis
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology*
  • Phosphorylation
  • Receptor, EphB4 / metabolism*
  • Receptor, EphB4 / physiology
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / physiology
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Ephrin-B2
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor, EphB4