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

Research output: Contribution to journalArticle

18 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

Fingerprint

epidermal growth factor
angiogenesis
Epidermal Growth Factor
blood vessels
Vascular Endothelial Growth Factor A
Blood Vessels
Assays
Chemical activation
assays
small interfering RNA
Small Interfering RNA
Endothelial cells
endothelial cells
Up-Regulation
Endothelial Cells
Neuropilin-1
Pathologic Neovascularization
Phosphorylation
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2

ASJC Scopus subject areas

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

Cite this

EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay. / Takeuchi, Kimio; Yanai, Ryoji; Kumase, Fumiaki; Morizane, Yuki; Suzuki, Jun; Kayama, Maki; Brodowska, Katarzyna; Nakazawa, Mitsuru; Miller, Joan W.; Connor, Kip M.; Vavvas, Demetrios G.

In: PLoS One, Vol. 9, No. 3, e91849, 19.03.2014.

Research output: Contribution to journalArticle

Takeuchi, K, Yanai, R, Kumase, F, Morizane, Y, Suzuki, J, Kayama, M, Brodowska, K, Nakazawa, M, Miller, JW, Connor, KM & Vavvas, DG 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, vol. 9, no. 3, e91849. https://doi.org/10.1371/journal.pone.0091849
Takeuchi, Kimio ; Yanai, Ryoji ; Kumase, Fumiaki ; Morizane, Yuki ; Suzuki, Jun ; Kayama, Maki ; Brodowska, Katarzyna ; Nakazawa, Mitsuru ; Miller, Joan W. ; Connor, Kip M. ; Vavvas, Demetrios G. / EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay. In: PLoS One. 2014 ; Vol. 9, No. 3.
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