Person: Kumase, Fumiaki
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Publication EGF-Like-Domain-7 Is Required for VEGF-Induced Akt/ERK Activation and Vascular Tube Formation in an Ex Vivo Angiogenesis Assay
(Public Library of Science, 2014) Takeuchi, Kimio; Yanai, Ryoji; Kumase, Fumiaki; Morizane, Yuki; Suzuki, Jun; Kayama, Maki; Brodowska, Katarzyna; Nakazawa, Mitsuru; Miller, Joan; Connor, Kip; Vavvas, DemetriosEGFL7 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.