Hepcidin in iron metabolism.
Hepcidin, which has been recently identified both by biochemical and genomic approaches, is a 25 amino acid polypeptide synthesized mainly by hepatocytes and secreted into the plasma. Besides its potential activity in antimicrobial defense, hepcidin plays a major role in iron metabolism. It controls two key steps of iron bioavailability, likely through a hormonal action: digestive iron absorption by enterocytes and iron recycling by macrophages. In humans, this could explain that low levels of hepcidin found during juvenile haemochromatosis and HFE-1 genetic haemochromatosis are associated with an iron overload phenotype. Conversely, an increase of hepcidin expression is suspected to play a major role in the development of anemia of chronic inflammatory diseases. However, the regulatory mechanisms of hepcidin expression are multiple, including iron-related parameters, anemia, hypoxia, inflammation and hepatocyte function. Therefore, many physiological and pathological situations may modulate hepcidin expression and subsequently iron metabolism. A better knowledge of the biological effects of hepcidin and of its expression regulatory mechanisms will clarify the place of hepcidin in the diagnosis and treatment of iron-related diseases.
Loréal
Olivier
O
INSERM U522, Hôpital Pontchaillou, 35033 Rennes Cedex, France. olivier.loreal@rennes.inserm.fr
Haziza-Pigeon
Christelle
C
Troadec
Marie-Bérengère
MB
Detivaud
Lénaïck
L
Turlin
Bruno
B
Courselaud
Brice
B
Ilyin
Guennadi
G
Brissot
Pierre
P
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007239:Infections / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007501:Iron / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D007501:Iron