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Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload

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Niederkofler, V.·2005·Journal of Clinical Investigation

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Abstract

Iron homeostasis plays a critical role in many physiological processes, notably synthesis of heme proteins. Dietary iron sensing and inflammation converge in the control of iron absorption and retention by regulating the expression of hepcidin, a regulator of the iron exporter ferroportin. Human mutations in the glycosylphosphatidylinositol-anchored protein hemojuvelin (HJV; also known as RGMc and HFE2) cause juvenile hemochromatosis, a severe iron overload disease, but the way in which HJV intersects with the iron regulatory network has been unclear. Here we show that, within the liver, mouse Hjv is selectively expressed by periportal hepatocytes and also that Hjv-mutant mice exhibit iron overload as well as a dramatic decrease in hepcidin expression. Our findings define a key role for Hjv in dietary iron sensing and also reveal that cytokine-induced inflammation regulates hepcidin expression through an Hjv-independent pathway.

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“Injection of LPS, a bacterial endotoxin and potent activator of inflammatory response, induces hepcidin in mice (8), an effect believed to be dependent on cytokine production (4, 5).”
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Authors: Niederkofler, V.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-08-01
Volume: 115
Issue: 8
Pages: 2180-2186
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci25683
OpenAlex: W2142833570
Cited by: 372
References: 11
FWCI: 14.99
Type: journal article
Language: en
Open access: bronze

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Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload

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