title: Molecular mechanisms regulating hepcidin revealed by hepcidin disorders.
abstract: Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (iron-refractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders.
authors.affiliation: Vita-Salute University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy. camaschella.clara@hsr.it
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
authors.forename: Laura
authors.initials: L
authors.lastname: Silvestri
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000502:physiology*; D006432:Hemochromatosis / Q000235:genetics; D064451:Hepcidins; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000502:physiology; D019189:Iron Metabolism Disorders / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D007501:Iron