Iron absorption and metabolism.
OBJECTIVE
Intestinal iron absorption is an essential physiological process that is regulated by the liver-derived peptide hepcidin. This review will describe recent advances in hepcidin biology and enterocyte iron transport.


RESULTS
Hepcidin acts as a repressor of iron absorption and its expression in turn reflects a range of systemic cues, including iron status, hypoxia, erythropoiesis and inflammation. These act through proteins on the hepatocyte plasma membrane such as HFE, hemojuvelin and transferrin receptor 2 to alter transcription of the hepcidin gene. Bone morphogenetic protein-SMAD signaling provides a key pathway of hepcidin activation, whereas the membrane-bound serine protease matriptase-2 and the erythroid factor growth differentiation factor 15 have emerged as important negative regulators of hepcidin expression. At the enterocyte itself, the recent demonstration of a chaperone for delivering iron to ferritin and new data on iron release from the hepcidin target ferroportin are helping to define the pathway of iron movement across the intestinal epithelium.


CONCLUSIONS
Disturbances in the hepcidin regulatory pathway underlie a range of iron metabolism disorders, from iron deficiency to iron loading, and there is considerable promise that the exciting recent advances in understanding hepcidin action will be translated into improved diagnostic and therapeutic modalities in the near future.
Anderson
Gregory J
GJ
Iron Metabolism Laboratory, Queensland Institute of Medical Research, University of Queensland, Brisbane, Queensland, Australia. Greg.Anderson@qimr.edu.au
Frazer
David M
DM
McLaren
Gordon D
GD
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D020895:Enterocytes / Q000378:metabolism; D005786:Gene Expression Regulation; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human