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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3332-3339 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation Fiona McLaughlin, Valerie J. Ludbrook, Joanne Cox, Ira von Carlowitz, Suzy Brown, and Anna M. Randi From the Cell Biology, CardioVascular Systems, and Genomics Units, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom; and Atugen, Boulder, CO. It has recently been shown that the transcription factor Erg, an Ets family member, drives constitutive expression of the intercellular adhesion molecule 2 (ICAM-2) in human umbilical vein endothelial cells (HUVECs) and that its expression is down-regulated by the pleiotropic cytokine tumor necrosis factor  (TNF-). To identify other Erg target genes and to define its function in the endothelium, a combined approach of antisense oligonucleotides (GeneBloc) and differential gene expression was used. Treatment of HUVECs with Erg-specific GeneBloc for 24, 48, and 72 hours suppressed Erg mRNA and protein levels at all time points. Total RNA extracted from HUVECs treated with Erg-specific or control GeneBloc was analyzed for differences in gene expression using high-density, sequence-verified cDNA arrays containing 482 relevant genes. Inhibition of Erg expression resulted in decreased expression of ICAM-2, as predicted. Four more genes decreased in Erg-deficient HUVECs were the extracellular matrix proteins SPARC and thrombospondin, the adhesive glycoprotein von Willebrand factor, and the small GTPase RhoA. Each of these molecules has been directly or indirectly linked to angiogenesis because of its role in vascular remodeling, adhesion, or shape change. Therefore, the role of Erg in vascular remodeling was tested in an in vitro model, and the results showed that HUVECs treated with Erg GeneBloc had a decreased ability to form tubulelike structures when grown on Matrigel. These results suggest that Erg may be a mediator of the TNF- effects on angiogenesis in vivo. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Yuan, V. Nikolova-Krstevski, Y. Zhan, M. Kondo, M. Bhasin, L. Varghese, K. Yano, C. V. Carman, W. C. Aird, and P. Oettgen Antiinflammatory Effects of the ETS Factor ERG in Endothelial Cells Are Mediated Through Transcriptional Repression of the Interleukin-8 Gene Circ. Res., May 8, 2009; 104(9): 1049 - 1057. [Abstract] [Full Text] [PDF] G. M. Birdsey, N. H. Dryden, V. Amsellem, F. Gebhardt, K. Sahnan, D. O. Haskard, E. Dejana, J. C. Mason, and A. M. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020