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Review
, 117 (17), 4425-33

Hepcidin and Iron Regulation, 10 Years Later

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Review

Hepcidin and Iron Regulation, 10 Years Later

Tomas Ganz. Blood.

Abstract

Under evolutionary pressure to counter the toxicity of iron and to maintain adequate iron supply for hemoglobin synthesis and essential metabolic functions, humans and other vertebrates have effective mechanisms to conserve iron and to regulate its concentration, storage, and distribution in tissues. The iron-regulatory hormone hepcidin, first described 10 years ago, and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron. Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes. Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron. Genetic malfunctions affecting the hepcidin-ferroportin axis are a main cause of iron overload disorders but can also cause iron-restricted anemias. Modulation of hepcidin and ferroportin expression during infection and inflammation couples iron metabolism to host defense and decreases iron availability to invading pathogens. This response also restricts the iron supply to erythropoietic precursors and may cause or contribute to the anemia associated with infections and inflammatory disorders.

Figures

Figure 1
Figure 1
Hepcidin interaction with ferroportin controls the main iron flows into plasma. Iron flows and reservoirs are depicted in blue, iron in hemoglobin in red, and hepcidin and its effect in orange. RBC indicates red blood cell; and Fpn, ferroportin.
Figure 2
Figure 2
A current model of regulation of hepcidin transcription by iron. Iron as holotransferrin is shown in orange, iron sensors and associated molecule in gray, BMP receptor and its transduction pathway in shades of blue, the ligands and coreceptors of the BMP receptor in shades of green, and the negative regulator protease in purple. *Molecules whose ablation was shown to cause iron dysregulation.

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