Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice.

Published

Journal Article

We report the generation of a tetracycline-regulated (Tet ON) transgenic mouse model for acute and chronic expression of the iron regulatory peptide hepcidin in the liver. We demonstrate that short-term and long-term tetracycline-dependent activation of hepcidin in adult mice leads to hypoferremia and iron-limited erythropoiesis, respectively. This clearly establishes the key role of hepcidin in regulating the extracellular iron concentration. We previously demonstrated that, when expressed early in fetal development, constitutive transgenic hepcidin expression prevented iron accumulation in an Hfe-/- mouse model of hemochromatosis. We now explore the effect of chronic hepcidin expression in adult Hfe-/- mice that have already developed liver iron overload. We demonstrate that induction of chronic hepcidin expression in 2-month-old Hfe-/- mice alters their pattern of cellular iron accumulation, leading to increased iron in tissue macrophages and duodenal cells but less iron in hepatocytes. These hepcidin-induced changes in the pattern of cellular iron accumulation are associated with decreased expression of the iron exporter ferroportin in macrophages but no detectable alteration of ferroportin expression in the hepatocytes. We speculate that this change in iron homeostasis could offer a therapeutic advantage by protecting against damage to parenchymal cells.

Full Text

Duke Authors

Cited Authors

  • Viatte, L; Nicolas, G; Lou, D-Q; Bennoun, M; Lesbordes-Brion, J-C; Canonne-Hergaux, F; Schönig, K; Bujard, H; Kahn, A; Andrews, NC; Vaulont, S

Published Date

  • April 1, 2006

Published In

Volume / Issue

  • 107 / 7

Start / End Page

  • 2952 - 2958

PubMed ID

  • 16339398

Pubmed Central ID

  • 16339398

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2005-10-4071

Language

  • eng

Conference Location

  • United States