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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5727-5733. Prepublished online as a Blood First Edition Paper on March 7, 2008; DOI 10.1182/blood-2007-08-106195. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-08-106195v1 111/12/5727    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 Pinto, J. P. Articles by Porto, G. Search for Related Content PubMed PubMed Citation Articles by Pinto, J. P. Articles by Porto, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 9, 2007 Accepted February 27, 2008 Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signalling and regulation of C/EBP Jorge P. Pinto, Sara Ribeiro, Helena Pontes, Shifaan Thowfeequ, David Tosh, Felix Carvalho, and Graca Porto* Iron Genes and Immune System, IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, Porto, Portugal Centre for Regenerative Medicine. Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom Clinical Hematology, Santo Antonio General Hospital, Porto, Portugal * Corresponding author; email: gporto{at}ibmc.up.pt. Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and re-mobilization of iron from intracellular stores. Recent in vivo studies have shown that hepcidin is down-regulated by erythropoiesis, anemia and hypoxia, which meets the need of iron input for erythrocyte production. Erythropoietin (EPO) is the primary signal that triggers erythropoiesis in anemic and hypoxic conditions. Therefore, a direct involvement of EPO in hepcidin regulation can be hypothesized. We report here the regulation of hepcidin expression by EPO, in a dose-dependent manner, in freshly isolated mouse hepatocytes and in the HepG2 human hepatocyte cell model. The effect is mediated through EPOR signaling, since hepcidin mRNA levels are restored by pre-treatment with an EPOR-blocking antibody. The transcription factor C/EBP showed a pattern of expression similar to hepcidin, at the mRNA and protein levels, following EPO and anti-EPOR treatments. Chromatin Immunoprecipitation experiments showed a significant decrease of C/EBP binding to the hepcidin promoter after EPO supplementation, suggesting the involvement of this transcription factor in the transcriptional response of hepcidin to EPO. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Valenti, D. Girelli, G. F. Valenti, A. Castagna, G. Como, N. Campostrini, R. Rametta, P. Dongiovanni, P. Messa, and S. Fargion HFE Mutations Modulate the Effect of Iron on Serum Hepcidin-25 in Chronic Hemodialysis Patients Clin. J. Am. Soc. Nephrol., August 1, 2009; 4(8): 1331 - 1337. [Abstract] [Full Text] [PDF] P. Robach, S. Recalcati, D. Girelli, C. Gelfi, N. J. Aachmann-Andersen, J. J. Thomsen, A. M. Norgaard, A. Alberghini, N. Campostrini, A. Castagna, et al. 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