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Pantelis A. Sarafidis, Adam Rumjon, Helen L. MacLaughlin, Iain C. Macdougall, Obesity and iron deficiency in chronic kidney disease: the putative role of hepcidin, Nephrology Dialysis Transplantation, Volume 27, Issue 1, January 2012, Pages 50–57, https://doi.org/10.1093/ndt/gfr686
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Hepcidin is a 25-amino acid peptide with a defensin-like structure that is primarily synthesized in hepatocytes [ 1 , 2 ]. It was independently isolated ∼10 years ago by two groups seeking peptides with antimicrobial activity in urine [ 3 ] and plasma [ 4 ]. Hepcidin was originally shown to have a weak selective antimicrobial activity against certain bacteria; thus, its name reflected the site of major tissue expression (‘hep’ for hepatocyte) and its antimicrobial properties (`cidin') [ 1 , 2 ]. However, soon after its isolation, independent studies suggested an important role of hepcidin in iron regulation [ 5 , 6 ]; currently, a large body of evidence strongly supports the role of hepcidin as the ‘master regulator’ of iron homeostasis [ 2 , 7 ].
Hepcidin reduces the efflux of recycled iron from both splenic and hepatic macrophages and also inhibits iron absorption from the gut [ 1 , 2 ] ( Figure 1 ). The cellular mechanisms of hepcidin action seem to be tissue specific. In reticuloendothelial macrophages, hepcidin was previously shown to bind to the cellular iron export channel ferroportin, inducing its internalization and subsequent degradation [ 8 , 9 ]. Recent data suggest that in intestinal epithelial cells, hepcidin mainly acts by decreasing the protein levels of the apical divalent metal transporter 1, another iron channel, through proteasome internalization and degradation [ 10–13 ]. A number of in vitro studies suggest that hepatic hepcidin transcription is upregulated by inflammatory cytokines, bone morphogenetic proteins (BMPs) and iron, and is downregulated by iron deficiency, hypoxia and ineffective erythropoiesis [ 14 , 15 ]. Thus, under physiological conditions, hepcidin acts by maintaining stable extracellular plasma iron concentrations and iron stores and also by providing adequate iron for erythropoiesis.
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