FGF-dependent regulation of VEGF receptor 2 expression in mice.
J Clin Invest, 2011/7;121(7):2668-78.
Murakami M[1], Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, Black BL, Simons M
Affiliations
PMID: 21633168
Impact factor: 19.456
Abstract
Numerous studies have suggested a link between the angiogenic FGF and VEGF signaling pathways; however, the nature of this link has not been established. To evaluate this relationship, we investigated VEGF signaling in ECs with disrupted FGF signaling in vitro and in vivo. ECs lacking FGF signaling became unresponsive to VEGF, caused by downregulation of VEGF receptor 2 (VEGFR2) expression after reduced Vegfr2 enhancer activation. FGF mediated VEGFR2 expression via activation of Erk1/2. Transcriptional analysis revealed that Ets transcription factors controlled VEGFR2 expression in an FGF- and Erk1/2-dependent manner. Mice with defective FGF signaling exhibited loss of vascular integrity and reduced vascular morphogenesis. Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF.
MeSH terms
Animals; Cells, Cultured; Endothelial Cells; Enzyme Activation; Fibroblast Growth Factors; Hindlimb; Humans; Ischemia; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neovascularization, Physiologic; Proto-Oncogene Proteins c-ets; Signal Transduction; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors
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