Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Apr 28;117(17):4425-33.
doi: 10.1182/blood-2011-01-258467. Epub 2011 Feb 23.

Hepcidin and iron regulation, 10 years later

Tomas Ganz  1
Affiliations
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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

References

    1. Krause A, Neitz S, Magert HJ, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000;480(2–3):147–150. - PubMed
    1. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276(11):7806–7810. - PubMed
    1. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276(11):7811–7819. - PubMed
    1. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A. 2001;98(15):8780–8785. - PMC - PubMed
    1. Andrews NC. Forging a field: the golden age of iron biology. Blood. 2008;112(2):219–230. - PMC - PubMed

Publication types