The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/beta-catenin signaling
File(s)
Published version
Author(s)
Type
Journal Article
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 (ErgcEC-KO) in mice causes embryonic lethality with vascular defects. Inducible endothelial deletion of ERG (ErgiEC-KO) results in defective physiological and pathological angiogenesis in the postnatal retina and tumors, with decreased vascular stability. ERG controls the Wnt/β-catenin pathway by promoting β-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 β-catenin levels, corrects vascular defects in ErgcEC-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.
Date Issued
2015-01-12
Date Acceptance
2014-11-10
Citation
Developmental Cell, 2015, 32 (1), pp.82-96
ISSN
1534-5807
Publisher
Elsevier
Start Page
82
End Page
96
Journal / Book Title
Developmental Cell
Volume
32
Issue
1
Copyright Statement
Copyright © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)
License URL
Sponsor
British Heart Foundation
British Heart Foundation
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347907200011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RG/11/17/29256
PG/10/94/28651
PG/09/096/28114
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Developmental Biology
PATHOLOGICAL ANGIOGENESIS
THERAPEUTIC ANGIOGENESIS
CELL DIFFERENTIATION
VE-CADHERIN
N-CADHERIN
IN-VIVO
GENE
PATHWAY
ACTIVATION
EXPRESSION
Publication Status
Published
Date Publish Online
2015-01-12