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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3133-3140. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-05-1695. This Article Full Text (PDF) All Versions of this Article: 2004-05-1695v1 105/8/3133    most recent Alert me when this article is cited Alert me if a correction is posted 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 Scortegagna, M. Articles by Garcia, J. A Search for Related Content PubMed PubMed Citation Articles by Scortegagna, M. Articles by Garcia, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 3, 2004 Accepted December 27, 2004 HIF-2 regulates murine hematopoietic development in an erythropoietin-dependent manner Marzia Scortegagna, Kan Ding, Quiyang Zhang, Yavuz Oktay, Michael J Bennett, Michael Bennett, John M Shelton, James A Richardson, Orson Moe, and Joseph A Garcia* Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA; Department of Pathology, Children's Medical Center, Dallas, TX, USA Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA * Corresponding author; email: joseph.garcia{at}utsouthwestern.edu. Erythropoiesis in the adult mammal depends critically upon erythropoietin, an inducible cytokine with pluripotent effects. Erythropoietin gene expression increases under conditions associated with lowered oxygen content such as anemia and hypoxia. HIF-1, the founding member of the hypoxia-inducible factor (HIF) alpha class, was identified by its ability to bind and activate the hypoxia-responsive enhancer in the erythropoietin regulatory region in vitro. The existence of multiple HIF alpha members raises the question of which HIF alpha member(s) regulate erythropoietin expression in vivo. We previously reported that mice lacking HIF-2, encoded by the EPAS1 gene, exhibit pancytopenia. In this study, we have characterized the etiology of this hematopoietic phenotype. Molecular studies of EPAS1 null kidneys reveal dramatically decreased erythropoietin gene expression. EPAS1 null as well as heterozygous mice have impaired renal erythropoietin induction in response to hypoxia. Treatment of EPAS1 null mice with exogenous erythropoietin reverses the hematopoietic and other defects. We propose that HIF-2 is an essential regulator of murine erythropoietin production. Impairments in HIF signaling, involving either HIF-1 or HIF-2, may play a prominent role in conditions involving altered hematopoietic or erythropoietin homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Siddiq, L. R. Aminova, C. M. Troy, K. Suh, Z. Messer, G. L. Semenza, and R. R. Ratan Selective Inhibition of Hypoxia-Inducible Factor (HIF) Prolyl-Hydroxylase 1 Mediates Neuroprotection against Normoxic Oxidative Death via HIF- and CREB-Independent Pathways J. Neurosci., July 8, 2009; 29(27): 8828 - 8838. [Abstract] [Full Text] [PDF] E. M. Dioum, R. Chen, M. S. Alexander, Q. Zhang, R. T. Hogg, R. D. Gerard, and J. A. Garcia Regulation of Hypoxia-Inducible Factor 2{alpha} Signaling by the Stress-Responsive Deacetylase Sirtuin 1 Science, June 5, 2009; 324(5932): 1289 - 1293. [Abstract] [Full Text] [PDF] T. Yamashita, O. Ohneda, A. Sakiyama, F. Iwata, K. Ohneda, and Y. Fujii-Kuriyama The microenvironment for erythropoiesis is regulated by HIF-2{alpha} through VCAM-1 in endothelial cells Blood, August 15, 2008; 112(4): 1482 - 1492. [Abstract] [Full Text] [PDF] E. M. Dioum, S. L. Clarke, K. Ding, J. J. Repa, and J. A. Garcia HIF-2{alpha}-Haploinsufficient Mice Have Blunted Retinal Neovascularization Due to Impaired Expression of a Proangiogenic Gene Battery Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2714 - 2720. [Abstract] [Full Text] [PDF] K. Takeda, H. L. Aguila, N. S. Parikh, X. Li, K. Lamothe, L.-J. Duan, H. Takeda, F. S. Lee, and G.-H. Fong Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins Blood, March 15, 2008; 111(6): 3229 - 3235. [Abstract] [Full Text] [PDF]

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