Regulation of hepcidin and iron-overload disease.
Hepcidin, a 25-amino-acid antimicrobial peptide, is the central regulator of iron homeostasis. Hepcidin transcription is upregulated by inflammatory cytokines, iron, and bone morphogenetic proteins and is downregulated by iron deficiency, ineffective erythropoiesis, and hypoxia. The iron transporter ferroportin is the cognate receptor of hepcidin and is destroyed as a result of interaction with the peptide. Except for inherited defects of ferroportin and hepcidin itself, all forms of iron-storage disease appear to arise from hepcidin dysregulation. Studies using multiple approaches have begun to delineate the molecular mechanisms that regulate hepcidin expression, particularly at the transcriptional level. Knowledge of the regulation of hepcidin by inflammation, iron, erythropoiesis, and hypoxia will lead to an understanding of the pathogenesis of primary hemochromatosis, secondary iron overload, and anemia of inflammatory disease.
Lee
Pauline L
PL
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. plee@scripps.edu
Beutler
Ernest
E
D000740:Anemia / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000378:metabolism; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D008565:Membrane Proteins; D000098742:Ferroportin; D007501:Iron