Regulation of iron metabolism by hepcidin.
Hepcidin, a peptide hormone made in the liver, is the principal regulator of systemic iron homeostasis. Hepcidin controls plasma iron concentration and tissue distribution of iron by inhibiting intestinal iron absorption, iron recycling by macrophages, and iron mobilization from hepatic stores. Hepcidin acts by inhibiting cellular iron efflux through binding to and inducing the degradation of ferroportin, the sole known cellular iron exporter. Synthesis of hepcidin is homeostatically increased by iron loading and decreased by anemia and hypoxia. Hepcidin is also elevated during infections and inflammation, causing a decrease in serum iron levels and contributing to the development of anemia of inflammation, probably as a host defense mechanism to limit the availability of iron to invading microorganisms. At the opposite side of the spectrum, hepcidin deficiency appears to be the ultimate cause of most forms of hemochromatosis, either due to mutations in the hepcidin gene itself or due to mutations in the regulators of hepcidin synthesis. The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
Nemeth
Elizabeta
E
Departments of Medicine and Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA. enemeth@mednet.ucla.edu
Ganz
Tomas
T
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D007501:Iron