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New insights into the regulation of iron homeostasis
Author(s) -
Deicher R.,
Hörl W. H.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01633.x
Subject(s) - hepcidin , hamp , ferroportin , proinflammatory cytokine , hemochromatosis , inflammation , microbiology and biotechnology , homeostasis , biology , endocrinology , chemistry , immunology , genetics
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 (the human leukocyte antigen‐related gene), TfR2 (the transferrin receptor‐2 gene) and HJV (the haemojuvelin gene) 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.