| Deletion of HIF-2α in the enterocytes decreases the severity of tissue iron loading in hepcidin knockout mice. | |
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MedLine Citation:
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PMID: 22128145 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Hereditary hemochromatosis (HH) is a highly prevalent genetic disorder characterized by excessive parenchymal iron accumulation leading to liver cirrhosis, diabetes and in some cases hepatocellular carcinoma. HH is caused by mutations in the genes encoding upstream regulators of hepcidin or more rarely in the hepcidin gene itself. A deficit in hepcidin results in intestinal iron hyperabsorption; however, the local effectors mediating the upregulation of iron absorption genes are unknown. We hypothesized that HIF-2 could mediate high iron absorption rates in HH. We generated Hepc(-/-) mice (a murine model of hemochromatosis) lacking HIF-2 in the intestine and showed that duodenal HIF-2 was essential for the upregulation of genes involved in intestinal iron import and the consequent iron accumulation in the liver and pancreas. This study highlights a role of HIF-2 in the dysregulation of iron absorption and chronic iron accumulation, as observed in patients with hemochromatosis. |
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Authors:
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Maria Mastrogiannaki; Pavle Matak; Stéphanie Delga; Jean-Christophe Deschemin; Sophie Vaulont; Carole Peyssonnaux |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-29 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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INSERM, U1016, Institut Cochin, Paris, France; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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