Hepcidin regulation: ironing out the details
Ivana De Domenico, … , Diane M. Ward, Jerry Kaplan
Ivana De Domenico, … , Diane M. Ward, Jerry Kaplan
Published July 2, 2007
Citation Information: J Clin Invest. 2007;117(7):1755-1758. https://doi.org/10.1172/JCI32701.
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Commentary

Hepcidin regulation: ironing out the details

Abstract

Hepcidin is a peptide hormone secreted by the liver that plays a central role in the regulation of iron homeostasis. Increased hepcidin levels result in anemia while decreased expression is the causative feature in most primary iron overload diseases. Mutations in hemochromatosis type 2 (HFE2), which encodes the protein hemojuvelin (HJV), result in the absence of hepcidin and an early-onset form of iron overload disease. HJV is a bone morphogenetic protein (BMP) coreceptor and HJV mutants have impaired BMP signaling. In this issue of the JCI, Babitt and colleagues show that BMPs are autocrine hormones that induce hepcidin expression (see the related article beginning on page 1933). Administration of a recombinant, soluble form of HJV decreased hepcidin expression and increased serum iron levels by mobilizing iron from splenic stores. These results demonstrate that recombinant HJV may be a useful therapeutic agent for treatment of the anemia of chronic disease, a disorder resulting from high levels of hepcidin expression.

Authors

Ivana De Domenico, Diane M. Ward, Jerry Kaplan

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Figure 1

Hepcidin-mediated regulation of iron homeostasis.

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Hepcidin-mediated regulation of iron homeostasis. (A) Increased hepcidin...
(A) Increased hepcidin expression by the liver results from inflammatory stimuli. High levels of hepcidin in the bloodstream result in the internalization and degradation of the iron exporter ferroportin. Loss of cell surface ferroportin results in macrophage iron loading, low plasma iron levels, and decreased erythropoiesis due to decreased transferrin-bound iron. The decreased erythropoiesis gives rise to the anemia of chronic disease. (B) Normal hepcidin levels, in response to iron demand, regulate the level of iron import into plasma, normal transferrin saturation, and normal levels of erythropoiesis. (C) Hemochromatosis, or iron overload, results from insufficient hepcidin levels, causing increased iron import into plasma, high transferrin saturation, and excess iron deposition in the liver.