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J Biol Chem. 2012 Feb 24;287(9):6582-91. doi: 10.1074/jbc.M111.300236. Epub 2012 Jan 10.

ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene.

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  • 1Division of Cardiology, Harvard Medical School, Boston, Massachusetts 02215, USA.

Abstract

ETS-related gene (ERG) is a member of the ETS transcription factor family. Our previous studies have shown that ERG expression is highly enriched in endothelial cells (EC) both in vitro and in vivo. ERG expression is markedly repressed in response to inflammatory stimuli. It has been shown that ERG is a positive regulator of several EC-restricted genes including VE-cadherin, endoglin, and von Willebrand factor, and a negative regulator of other genes such as interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1. In this study we have identified a novel role for ERG in the regulation of EC barrier function. ERG knockdown results in marked increases in EC permeability. This is associated with a significant increase of stress fiber and gap formation in EC. Furthermore, we identify CLDN5 as a downstream target of ERG in EC. Thus, our results suggest that ERG plays a pivotal role in regulating EC barrier function and that this effect is mediated in part through its regulation of CLDN5 gene expression.

PMID:
22235125
PMCID:
PMC3307294
DOI:
10.1074/jbc.M111.300236
[PubMed - indexed for MEDLINE]
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