EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay

Kimio Takeuchi, Ryoji Yanai, Fumiaki Kumase, Yuki Morizane, Jun Suzuki, Maki Kayama, Katarzyna Brodowska, Mitsuru Nakazawa, Joan W. Miller, Kip M. Connor, Demetrios G. Vavvas

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19 Citations (Scopus)

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.

Original languageEnglish
Article numbere91849
JournalPloS one
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 19 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Takeuchi, K., Yanai, R., Kumase, F., Morizane, Y., Suzuki, J., Kayama, M., Brodowska, K., Nakazawa, M., Miller, J. W., Connor, K. M., & Vavvas, D. G. (2014). EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay. PloS one, 9(3), [e91849]. https://doi.org/10.1371/journal.pone.0091849