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Blood, 1 July 2004, Vol. 104, No. 1, pp. 149-158. Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2004-01-0273. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0273v1 104/1/149    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hesser, B. A. Articles by Gerber, H.-P. Search for Related Content PubMed PubMed Citation Articles by Hesser, B. A. Articles by Gerber, H.-P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Signal Transduction Gene Expression Genomics Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells Boris A. Hesser, Xiao Huan Liang, Gieri Camenisch, Suya Yang, David A. Lewin, Richard Scheller, Napoleone Ferrara, and Hans-Peter Gerber From the Department of Molecular Oncology, Genentech, South San Francisco, CA; and CuraGen, Branford, CT. We conducted a genome-wide analysis of genes that are regulated by vascular endothelial growth factor (VEGF) in endothelial cells and identified DSCR1 to be most significantly induced. Consistent with an antagonistic function on calcineurin (CnA) signaling, expression of DSCR1 in endothelial cells blocked dephosphorylation, nuclear translocation, and activity of nuclear factor of activated T cell (NFAT), a transcription factor involved in mediating CnA signaling. DSCR1 was not only induced by VEGF, but also by other compounds activating CnA signaling, suggesting a more general role for DSCR1 in activated endothelial cells. Transient expression of DSCR1 attenuated inflammatory marker genes such as tissue factor (TF), E-selectin, and Cox-2, identifying a previously unknown regulatory role for DSCR1 in activated endothelial cells. In contrast, knock-down of endogenous DSCR1 increased NFAT activity and stimulated expression of inflammatory genes on activated endothelial cells. Thus, the negative regulatory feedback loop between DSCR1 and CnA signaling in endothelial cells identified may represent a potential molecular mechanism underlying the frequently transient expression of inflammatory genes following activation of endothelial cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: VEGF up-regulates DSCR1: more surprises Michael Detmar Blood 2004 104: 6-7. [Full Text] [PDF] This article has been cited by other articles: M. L. Calicchio, T. Collins, and H. P. Kozakewich Identification of Signaling Systems in Proliferating and Involuting Phase Infantile Hemangiomas by Genome-Wide Transcriptional Profiling Am. J. Pathol., May 1, 2009; 174(5): 1638 - 1649. [Abstract] [Full Text] [PDF] M. C. Mulero, A. Aubareda, M. Orzaez, J. Messeguer, E. Serrano-Candelas, S. Martinez-Hoyer, A. Messeguer, E. Perez-Paya, and M. 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