{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:26:29Z","timestamp":1774423589642,"version":"3.50.1"},"reference-count":36,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization 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 pretreatment with an EPOR-blocking antibody. The transcription factor C\/EBP\u03b1 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\u03b1 binding to the hepcidin promoter after EPO supplementation, suggesting the involvement of this transcription factor in the transcriptional response of hepcidin to EPO.<\/jats:p>","DOI":"10.1182\/blood-2007-08-106195","type":"journal-article","created":{"date-parts":[[2008,3,8]],"date-time":"2008-03-08T02:48:43Z","timestamp":1204944523000},"page":"5727-5733","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":187,"title":["Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C\/EBP\u03b1"],"prefix":"10.1182","volume":"111","author":[{"given":"Jorge P.","family":"Pinto","sequence":"first","affiliation":[{"name":"Iron Genes and Immune System, Instituto de Biologia Molecular e Celular (IBMC), University of Porto, Porto, Portugal;"}]},{"given":"Sara","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Iron Genes and Immune System, Instituto de Biologia Molecular e Celular (IBMC), University of Porto, Porto, Portugal;"}]},{"given":"Helena","family":"Pontes","sequence":"additional","affiliation":[{"name":"REQUIMTE (Rede de Qu\u00edmica e Tecnologia), Toxicology Department, Faculty of Pharmacy, University of Porto, Porto, Portugal;"}]},{"given":"Shifaan","family":"Thowfeequ","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom;"}]},{"given":"David","family":"Tosh","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom;"}]},{"given":"F\u00e9lix","family":"Carvalho","sequence":"additional","affiliation":[{"name":"REQUIMTE (Rede de Qu\u00edmica e Tecnologia), Toxicology Department, Faculty of Pharmacy, University of Porto, Porto, Portugal;"}]},{"given":"Gra\u00e7a","family":"Porto","sequence":"additional","affiliation":[{"name":"Iron Genes and Immune System, Instituto de Biologia Molecular e Celular (IBMC), University of Porto, Porto, Portugal;"},{"name":"Clinical Hematology, Santo Ant\u00f3nio General Hospital, Porto, Portugal; and"},{"name":"Molecular Immunology and Pathology, Abel Salazar Institute for the Biomedical Science (ICBAS), University of Porto, Porto, Portugal"}]}],"member":"234","reference":[{"key":"2019111713451166800_B1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.nutr.26.061505.111303","article-title":"Regulation of iron metabolism by hepcidin.","volume":"26","author":"Nemeth","year":"2006","journal-title":"Annu Rev Nutr"},{"key":"2019111713451166800_B2","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.","volume":"306","author":"Nemeth","year":"2004","journal-title":"Science"},{"key":"2019111713451166800_B3","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1182\/blood.V84.6.1697.1697","article-title":"Regulators of iron balance in humans.","volume":"84","author":"Finch","year":"1994","journal-title":"Blood"},{"key":"2019111713451166800_B4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1365-2362.2005.01525.x","article-title":"Regulation of erythropoietin production.","volume":"35","author":"Eckardt","year":"2005","journal-title":"Eur J Clin Invest"},{"key":"2019111713451166800_B5","first-page":"F474","article-title":"Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia.","volume":"263","author":"Tan","year":"1992","journal-title":"Am J Physiol"},{"key":"2019111713451166800_B6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/bcmd.2002.0573","article-title":"Hepcidin, a new iron regulatory peptide.","volume":"29","author":"Nicolas","year":"2002","journal-title":"Blood Cells Mol Dis"},{"key":"2019111713451166800_B7","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.peptides.2007.01.016","article-title":"Regulation of hepcidin in HepG2 and RINm5F cells.","volume":"28","author":"Fein","year":"2007","journal-title":"Peptides"},{"key":"2019111713451166800_B8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1182\/blood-2002-11-3610","article-title":"Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron.","volume":"102","author":"Gehrke","year":"2003","journal-title":"Blood"},{"key":"2019111713451166800_B9","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1093\/carcin\/bgg060","article-title":"Erythropoietin regulates tumour growth of human malignancies.","volume":"24","author":"Yasuda","year":"2003","journal-title":"Carcinogenesis"},{"key":"2019111713451166800_B10","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1182\/blood-2007-04-087593","article-title":"Iron-transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2\/4.","volume":"110","author":"Lin","year":"2007","journal-title":"Blood"},{"key":"2019111713451166800_B11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0076-6879(78)52006-5","article-title":"Isolation and use of liver cells.","volume":"52","author":"Mold\u00e9us","year":"1978","journal-title":"Methods Enzymol"},{"key":"2019111713451166800_B12","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s002040000200","article-title":"Is hyperthermia the triggering factor for hepatotoxicity induced by 3,4-methylenedioxymethamphetamine (ecstasy)? an in vitro study using freshly isolated mouse hepatocytes.","volume":"74","author":"Carvalho","year":"2001","journal-title":"Arch Toxicol"},{"key":"2019111713451166800_B13","doi-asserted-by":"crossref","first-page":"5651","DOI":"10.1523\/JNEUROSCI.1288-04.2004","article-title":"Constitutive overexpression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration.","volume":"24","author":"Grimm","year":"2004","journal-title":"J Neurosci"},{"key":"2019111713451166800_B14","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1365-2141.1990.tb06377.x","article-title":"Effects of recombinant human erythropoietin on hemolytic anaemia in mice.","volume":"76","author":"Cynshi","year":"1990","journal-title":"Br J Haematol"},{"key":"2019111713451166800_B15","first-page":"36","article-title":"Image processing with Image","volume":"11","author":"Abramoff","year":"2004","journal-title":"J. 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