Karin E Finberg1. 1. Duke University Medical Center, Durham, North Carolina 27710, USA. karin.finberg@duke.edu
Abstract
PURPOSE OF REVIEW: The circulating peptide hepcidin modulates systemic iron balance by limiting the absorption of dietary iron and the release of iron from macrophage stores. Recent studies conducted in humans, animal models, and tissue culture systems have enhanced our understanding of the molecular mechanisms by which hepcidin levels are altered in response to iron stores, inflammation, and erythropoietic activity. RECENT FINDINGS: The bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 play key, nonredundant roles in mediating hepcidin synthesis through the BMP signaling pathway. Actions of the hereditary hemochromatosis proteins HFE and transferrin receptor 2 may intersect with the BMP pathway. Hepcidin induction in response to inflammation requires cooperative BMP signaling. A variety of innate immune and infectious stimuli induce hepcidin expression. The hypoxia inducible factor pathway appears to suppress hepcidin indirectly through the capacity of erythropoietin to stimulate erythropoiesis. SUMMARY: Study of the molecular mechanisms underlying the regulation of hepcidin synthesis has revealed complex biology. Improved understanding of the signaling pathways involved in hepcidin regulation may contribute to improved therapeutic outcomes for patients with genetic and acquired disorders that impact systemic iron balance.
PURPOSE OF REVIEW: The circulating peptide hepcidin modulates systemic iron balance by limiting the absorption of dietary iron and the release of iron from macrophage stores. Recent studies conducted in humans, animal models, and tissue culture systems have enhanced our understanding of the molecular mechanisms by which hepcidin levels are altered in response to iron stores, inflammation, and erythropoietic activity. RECENT FINDINGS: The bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 play key, nonredundant roles in mediating hepcidin synthesis through the BMP signaling pathway. Actions of the hereditary hemochromatosis proteins HFE and transferrin receptor 2 may intersect with the BMP pathway. Hepcidin induction in response to inflammation requires cooperative BMP signaling. A variety of innate immune and infectious stimuli induce hepcidin expression. The hypoxia inducible factor pathway appears to suppress hepcidin indirectly through the capacity of erythropoietin to stimulate erythropoiesis. SUMMARY: Study of the molecular mechanisms underlying the regulation of hepcidin synthesis has revealed complex biology. Improved understanding of the signaling pathways involved in hepcidin regulation may contribute to improved therapeutic outcomes for patients with genetic and acquired disorders that impact systemic iron balance.