TY - JOUR
T1 - ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene
AU - Yuan, Lei
AU - Le Bras, Alexandra
AU - Sacharidou, Anastasia
AU - Itagaki, Kiyoshi
AU - Zhan, Yumei
AU - Kondo, Maiko
AU - Carman, Christopher V.
AU - Davis, George E.
AU - Aird, William C.
AU - Oettgen, Peter
PY - 2012/2/24
Y1 - 2012/2/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857468365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857468365&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.300236
DO - 10.1074/jbc.M111.300236
M3 - Article
C2 - 22235125
AN - SCOPUS:84857468365
SN - 0021-9258
VL - 287
SP - 6582
EP - 6591
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -