Editors' ChoicePhysiology

Iron Homeostasis

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Science's STKE  24 Jul 2001:
Vol. 2001, Issue 92, pp. tw6
DOI: 10.1126/stke.2001.92.tw6

Hemochromatosis (HH) is a human disease characterized by an overload of iron in the plasma and multiple organs. The mouse model of HH is the result of a mutation in the HFE gene, which encodes a protein that interacts with the transferrin receptor. Maintaining iron homeostasis involves regulating absorption of dietary iron, its transport, and its storage. However, the signals that regulate these processes are not known. Nicolas et al. report that a peptide normally expressed in the plasma and liver called hepcidin may be a candidate iron sensor. Hepcidin was absent in mice that no longer expressed USF2, a transcription factor involved in gene expression in the liver. These mice displayed an HH-like phenotype, suggesting that the peptide is somehow involved in regulating iron levels. Splenic macrophages, which normally store iron, were also depleted of iron in these mice. However, the expression of several proteins implicated in iron transport was normal. The authors speculate that hepcidin might regulate the expression of iron transporters in intestinal enterocytes and splenic macrophages.

G. Nicolas, M. Bennoun, I. Devaux, C. Beaumont, B. Grandchamp, A. Kahn, S. Vaulont, 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. 98, 8780-8785 (2001). [Abstract] [Full Text]

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