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

Lei Yuan, Alexandra Le Bras, Anastasia Sacharidou, Kiyoshi Itagaki, Yumei Zhan, Maiko Kondo, Christopher V. Carman, George E. Davis, William C. Aird, Peter Oettgen

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6582-6591
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number9
DOIs
StatePublished - Feb 24 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yuan, L., Le Bras, A., Sacharidou, A., Itagaki, K., Zhan, Y., Kondo, M., Carman, C. V., Davis, G. E., Aird, W. C., & Oettgen, P. (2012). ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene. Journal of Biological Chemistry, 287(9), 6582-6591. https://doi.org/10.1074/jbc.M111.300236