Downregulation of Fes inhibits VEGF-A-induced chemotaxis and capillary-like morphogenesis by cultured endothelial cells.
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.
Kanda
Shigeru
S
Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. skanda-jua@umin.net
Kanetake
Hiroshi
H
Miyata
Yasuyoshi
Y
D002196:Capillaries / Q000187:drug effects / Q000196:embryology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496645:FES protein, human; D051578:Proto-Oncogene Proteins c-fes; D051057:Proto-Oncogene Proteins c-akt