title: Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron.
abstract: Experimental data suggest the antimicrobial peptide hepcidin as a central regulator in iron homeostasis. In this study, we characterized the expression of human hepcidin in experimental and clinical iron overload conditions, including hereditary hemochromatosis. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we determined expression of hepcidin and the most relevant iron-related genes in liver biopsies from patients with hemochromatosis and iron-stain-negative control subjects. Regulation of hepcidin mRNA expression in response to transferrin-bound iron, non-transferrin-bound iron, and deferoxamine was analyzed in HepG2 cells. Hepcidin expression correlated significantly with serum ferritin levels in controls, whereas no significant up-regulation was observed in patients with hemochromatosis despite iron-overload conditions and high serum ferritin levels. However, patients with hemochromatosis showed an inverse correlation between hepcidin transcript levels and the serum transferrin saturation. Moreover, we found a significant correlation between hepatic transcript levels of hepcidin and transferrin receptor-2 irrespective of the iron status. In vitro data indicated that hepcidin expression is down-regulated in response to non-transferrin-bound iron. In conclusion, the presented data suggest a close relationship between the transferrin saturation and hepatic hepcidin expression in hereditary hemochromatosis. Although the causality is not yet clear, this interaction might result from a down-regulation of hepcidin expression in response to significant levels of non-transferrin-bound iron.
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Bergheimer Strasse 58, 69115 Heidelberg, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Gehrke
authors.forename: Hasan
authors.initials: H
authors.lastname: Kulaksiz
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Riedel
authors.forename: Karin
authors.initials: K
authors.lastname: Bents
authors.forename: Claudia
authors.initials: C
authors.lastname: Veltkamp
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D005192:Family Health; D005786:Gene Expression Regulation; D006432:Hemochromatosis / Q000378:metabolism* / Q000473:pathology; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000097:blood; D008099:Liver / Q000473:pathology; D012313:RNA / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis / Q000235:genetics; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D011990:Receptors, Transferrin; D014168:Transferrin; D012313:RNA; D007501:Iron