Iron regulation and erythropoiesis.
OBJECTIVE
The peptide hormone hepcidin regulates iron metabolism in response to erythropoietic demand, iron stores and inflammation. Major advances have been made in understanding the regulation of hepcidin production, and consequently the availability of iron for erythropoiesis.


RESULTS
It is becoming clear that the bone morphogenetic protein (BMP) pathway plays a major role in setting the baseline hepcidin level and, with the assistance of BMP2/4 and hemochromatosis-related proteins hemojuvelin, HFE and transferrin receptor 2, also regulates hepcidin expression in response to iron. Regulation of hepcidin in anemias has now been linked to increased erythropoietic activity and is likely mediated by factor(s) secreted by erythroid precursors. GDF-15 was identified as a candidate for one of the erythroid factors suppressing hepcidin. Tissue hypoxia may also directly contribute to hepcidin suppression in anemias. Regulation of hepcidin by inflammation may include multiple cytokines and the Toll-like receptors pathways. Although it has not yet been shown that increased hepcidin is indispensible for the development of anemia of inflammation, transgenic overexpression of hepcidin was sufficient to replicate its key features.


CONCLUSIONS
Regulation of hepcidin and iron availability for erythropoiesis has revealed unexpected pathways and much complexity. The renaissance of the study of iron regulation continues to reward researchers with interesting biology and potential therapeutic targets.
Nemeth
Elizabeta
E
David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. enemeth@mednet.ucla.edu
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000503:physiopathology*; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D019485:Bone Morphogenetic Proteins; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D000098742:Ferroportin; D007501:Iron