title: ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene.
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.
authors.affiliation: Division of Cardiology, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Le Bras
authors.forename: Anastasia
authors.initials: A
authors.lastname: Sacharidou
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Itagaki
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhan
authors.forename: Maiko
authors.initials: M
authors.lastname: Kondo
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Carman
authors.forename: George E
authors.initials: GE
authors.lastname: Davis
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
authors.forename: Peter
authors.initials: P
authors.lastname: Oettgen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D062507:Claudin-5; D057167:Claudins / Q000235:genetics*; D003331:Coronary Vessels / Q000166:cytology; D003599:Cytoskeleton / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D055806:Microvessels / Q000166:cytology; D016297:Mutagenesis, Site-Directed; D011651:Pulmonary Artery / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D000071230:Transcriptional Regulator ERG; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014409:Tumor Necrosis Factor-alpha