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The transcription factor Erg regulates angiogenesis and endothelial apoptosis
Author(s) -
RANDI ANNA MARIA,
Birdsey Graeme,
Dryden Nicola,
Amsellem Valerie,
Gebhardt Frank,
Haskard Dorian,
Dejana Elisabetta,
Mason Justin Charles
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.471.8
Subject(s) - erg , angiogenesis , ets transcription factor family , matrigel , chromatin immunoprecipitation , biology , transcription factor , microbiology and biotechnology , apoptosis , cancer research , gene expression , promoter , retina , gene , genetics , neuroscience
Tight regulation of the balance between apoptosis and survival is essential in angiogenesis. The Ets transcription factor Erg is required for angiogenesis. Inhibition of Erg expression in human umbilical vein endothelial cells (HUVEC) using antisense resulted in detachment of cell‐cell contacts. A key regulator of junction stability in EC is VE‐cadherin. Using chromatin immunoprecipitation (ChIP), we found that Erg binds the VE‐cadherin promoter in HUVEC; moreover, inhibition of Erg expression in HUVEC resulted in a significant decrease in VE‐cadherin levels. Both Erg and VE‐cadherin provide survival signals to EC; apoptosis induced by inhibition of Erg was partly rescued by over‐expression of VE‐cadherin‐GFP, suggesting that VE‐cadherin is involved in the Erg‐dependent survival signals. Additional survival signals mediated by Erg may be via the anti‐apoptotic molecule Bcl‐2, since Erg binds the Bcl‐2 promoter and inhibition of Erg expression in HUVEC results in decreased Bcl‐2 levels. To validate the role of Erg in angiogenesis in vivo, we used Erg siRNA in a Matrigel plug model. Matrigel, mixed with bFGF and either Erg or control siRNA, was injected subcutaneously in mice. Erg inhibition resulted in a significant decrease in vascularization of the plugs, as measured by H&E and CD34 staining. These results identify a new pathway regulating angiogenesis via Erg, VE‐cadherin and endothelial survival. Research supported by the British Heart Foundation