Year: 2011
Type: article
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.
DOI: 10.1172/jci44762
Institutions: Yale University, University of California, San Francisco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Yale University, Wake Forest University, Dartmouth College, National Institutes of Health, Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences, Yale University, National Heart, Lung, and Blood Institute, National Institute of Dental and Craniofacial Research
OpenAlex ID: W2028172989