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Mode d'action de l'hepcidine, nouvelle hormone du métabolisme du fer, et son implication dans l'hémochromatose

Abstract : Iron is essential for the organism but iron excess can be deleterious. Iron overload diseases are frequent and called hemochromatosis. Hereditary hemochromatosis is an autosomal recessive disease and generally due to mutations in HFE gene. Hepcidin is a small peptide produced by the liver in response to iron load that inhibits intestinal iron absorption and recycling of iron by macrophages.
In order to get insights about hepcidin mode of action we used hepcidin deficient mice. These mice present massive iron overload resembling iron overload observed in hereditary hemochromatosis. We observed that there was an increase in levels of proteins involved in intestinal iron absorption and of ferroportin in the duodenum, spleen and liver in these mice.
We then wanted to test the therapeutic role of hepcidin in hemochromatosis. We demonstrated that transgenic hepcidin was able to prevent iron overload in Hfe KO mice. We next developed a murine model inducibly expressing hepcidin and observed that induction of
transgenic hepcidin in iron loaded Hfe KO mice altered iron distribution. Iron accumulated in enterocytes and macrophages rather than in hepatocytes and this retention of iron was associated with a decrease in ferroportin protein levels. We thus demonstrated that hepcidin could not only prevent but also cure iron overload in HFE-hemochromatosis.
Hepcidin seems to play a major role in hemochromatosis aetiology and could be a key therapeutic agent for this disease.
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Contributor : Lydie Viatte <>
Submitted on : Wednesday, March 4, 2009 - 3:37:10 PM
Last modification on : Thursday, April 9, 2020 - 11:53:35 AM
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  • HAL Id : tel-00365791, version 1

Citation

Lydie Viatte. Mode d'action de l'hepcidine, nouvelle hormone du métabolisme du fer, et son implication dans l'hémochromatose. Physiologie [q-bio.TO]. Université Paris-Diderot - Paris VII, 2006. Français. ⟨tel-00365791⟩

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