Downregulation of Fes inhibits VEGF-A-induced chemotaxis and capillary-like morphogenesis by cultured endothelial cells

J Cell Mol Med. May-Jun 2007;11(3):495-501. doi: 10.1111/j.1582-4934.2007.00034.x.

Abstract

The aim of this study was to determine whether the downregulation of endogenous Fes by siRNA in cultured endothelial cells affects vascular endothelial growth factor-A (VEGF-A)-induced chemotaxis and capillary-like morphogenesis, which are considered as angiogenic cellular responses in vitro. VEGF-A-treatment induced autophosphorylation of Fes in cultured endothelial cells. LY294002, a phosphoinositide 3-kinase inhibitor, significantly inhibited VEGF-A-induced chemotaxis and capillary-like morphogenesis. Downregulation of Fes attenuated these VEGF-A-induced cellular responses but LY294002 did not produce further inhibition of these responses. Downregulation of Fes neither affected VEGF-A-induced autophosphorylation of VEGF receptor 2 nor mitogen-activated protein kinase activation, but markedly decreased Akt activation. Taken together, our novel results indicate the involvement of Fes in VEGF-A-induced cellular responses by cultured endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillaries / drug effects
  • Capillaries / embryology*
  • Cells, Cultured
  • Chemotaxis / drug effects*
  • Down-Regulation / drug effects*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / metabolism*
  • Enzyme Activation / drug effects
  • Humans
  • Models, Biological
  • Morphogenesis / drug effects*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-fes / genetics*
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Umbilical Veins / enzymology
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • RNA, Small Interfering
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • FES protein, human
  • Proto-Oncogene Proteins c-fes
  • Proto-Oncogene Proteins c-akt