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The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling

Item Type:Article
Title:The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling
Creators Name:Birdsey, G.M. and Shah, A.V. and Dufton, N. and Reynolds, L.E. and Osuna Almagro, L. and Yang, Y. and Aspalter, I.M. and Khan, S.T. and Mason, J.C. and Dejana, E. and Göttgens, B. and Hodivala-Dilke, K. and Gerhardt, H. and Adams, R.H. and Randi, A.M.
Abstract:Blood vessel stability is essential for embryonic development; in the adult, many diseases are associated with loss of vascular integrity. The ETS transcription factor ERG drives expression of VE-cadherin and controls junctional integrity. We show that constitutive endothelial deletion of ERG (Erg(cEC-KO)) in mice causes embryonic lethality with vascular defects. Inducible endothelial deletion of ERG (Erg(iEC-KO)) results in defective physiological and pathological angiogenesis in the postnatal retina and tumors, with decreased vascular stability. ERG controls the Wnt/{beta}-catenin pathway by promoting {beta}-catenin stability, through signals mediated by VE-cadherin and the Wnt receptor Frizzled-4. Wnt signaling is decreased in ERG-deficient endothelial cells; activation of Wnt signaling with lithium chloride, which stabilizes {beta}-catenin levels, corrects vascular defects in Erg(cEC-KO) embryos. Finally, overexpression of ERG in vivo reduces permeability and increases stability of VEGF-induced blood vessels. These data demonstrate that ERG is an essential regulator of angiogenesis and vascular stability through Wnt signaling.
Keywords:{beta} Catenin, Cadherins, CD Antigens, Chromatin Immunoprecipitation, Cultured Cells, Frizzled Receptors, Human Umbilical Vein Endothelial Cells, Integrases, Lung, Oncogene Proteins, Physiologic Neovascularization, Pregnancy, Real-Time Polymerase Chain Reaction, Signal Transduction, Transcription Factors, Transgenic Mice, Vascular Endothelial Growth Factor A, Vascular Endothelium, Western Blotting, Wnt Proteins, Animals, Mice
Source:Developmental Cell
Publisher:Cell Press / Elsevier
Page Range:82-96
Date:12 January 2015
Official Publication:https://doi.org/10.1016/j.devcel.2014.11.016
PubMed:View item in PubMed

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