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EGF-Like-Domain-7 Is Required for VEGF-Induced Akt/ERK Activation and Vascular Tube Formation in an Ex Vivo Angiogenesis Assay

Author

Listed:
  • 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

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.

Suggested Citation

  • 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, 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, Public Library of Science, vol. 9(3), pages 1-7, March.
    • Handle: RePEc:plo:pone00:0091849
    DOI: 10.1371/journal.pone.0091849
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    1. Werner Risau, 1997. "Mechanisms of angiogenesis," Nature, Nature, vol. 386(6626), pages 671-674, April.
    2. Peter Carmeliet & Rakesh K. Jain, 2000. "Angiogenesis in cancer and other diseases," Nature, Nature, vol. 407(6801), pages 249-257, September.
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