The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling
Authors
- G.M. Birdsey
- A.V. Shah
- N. Dufton
- L.E. Reynolds
- L. Osuna Almagro
- Y. Yang
- I.M. Aspalter
- S.T. Khan
- J.C. Mason
- E. Dejana
- B. Göttgens
- K. Hodivala-Dilke
- H. Gerhardt
- R.H. Adams
- A.M. Randi
Journal
- Developmental Cell
Citation
- Dev Cell 32 (1): 82-96
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.