Unique signal transduction of the VEGF family members VEGF-A and VEGF-E.
Both VEGF (vascular endothelial growth factor)-A and Orf-virus-encoded VEGF-E bind and activate VEGFR (VEGF receptor)-2; however, only VEGF-A binds VEGFR-1. To understand the biological differences between VEGF-A and VEGF-E in vivo, we established transgenic mouse models. K14 (keratin-14)-promoter-driven VEGF-E transgenic mice showed a significant increase in mature blood vessels. However, K14-VEGF-A transgenic mice exhibited severe inflammation and oedema with increased angiogenesis, as well as lymphangiogenesis and lymph vessel dilatation. K14-VEGF-A transgenic mice deficient in VEGFR-1 signalling (K14-VEGF-A-tg/VEGFR-1 TK(-/-) mice) showed decreases in oedema and inflammation with less recruitment of macrophage-lineage cells, suggesting an involvement of VEGFR-1 in these adverse effects. VEGFE might be more useful than VEGFA for pro-angiogenic therapy.
Shibuya
Masabumi
M
Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. shibuya@ims.u-tokyo.ac.jp
D000818:Animals; D003435:Crotalid Venoms / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D003435:Crotalid Venoms; D053547:Keratin-14; D020033:Protein Isoforms; C029748:Trimeresurus venoms; C084758:VEGF-like protein, Orf virus; D042461:Vascular Endothelial Growth Factor A; D014764:Viral Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2