title: New insights into the regulation of iron homeostasis.
abstract: Hepcidin evolves as a potent hepatocyte-derived regulator of the body's iron distribution piloting the flow of iron via, and directly binding, to the cellular iron exporter ferroportin. The hepcidin-ferroportin axis dominates the iron egress from all cellular compartments that are critical to iron homeostasis, namely placental syncytiotrophoblasts, duodenal enterocytes, hepatocytes and macrophages of the reticuloendothelial system. The gene that encodes hepcidin expression (HAMP) is subject to regulation by proinflammatory cytokines, such as IL-6 and IL-1; excessive hepcidin production explains the relative deficiency of iron during inflammatory states, eventually resulting in the anaemia of inflammation. The haemochromatosis genes HFE, TfR2 and HJV potentially facilitate the transcription of HAMP. Disruption of each of the four genes leads to a diminished hepatic release of hepcidin consistent with both a dominant role of hepcidin in hereditary haemochromatosis and an upstream regulatory role of HFE, TfR2 and HJV on HAMP expression. The engineered generation of hepcidin agonists, mimetics or antagonists could largely broaden current therapeutic strategies to redirect the flow of iron.
authors.affiliation: Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Deicher
authors.forename: W H
authors.initials: WH
authors.lastname: Hörl
mesh_terms: D000740:Anemia / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000502:physiology; D027682:Cation Transport Proteins / Q000502:physiology; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D000098742:Ferroportin; D007501:Iron