@article {1351200,
	title = {EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay},
	journal = {PLoS One},
	volume = {9},
	number = {3},
	year = {2014},
	month = {2014},
	pages = {e91849},
	abstract = {EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.},
	keywords = {Animals, Biological Assay, Endothelial Cells, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Gene Knockdown Techniques, In Vitro Techniques, Mice, Inbred C57BL, Neovascularization, Physiologic, Neuropilin-1, Phosphorylation, Proteins, Proto-Oncogene Proteins c-akt, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0091849},
	author = {Takeuchi, Kimio and Yanai, Ryoji and Kumase, Fumiaki and Morizane, Yuki and Suzuki, Jun and Kayama, Maki and Brodowska, Katarzyna and Nakazawa, Mitsuru and Miller, Joan W and Connor, Kip M and Vavvas, Demetrios G}
}
