Abstract |
Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with beta-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in beta-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in beta-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.
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Authors | Sara Gardenghi, Pedro Ramos, Antonia Follenzi, Niva Rao, Eliezer A Rachmilewitz, Patricia J Giardina, Robert W Grady, Stefano Rivella |
Journal | Annals of the New York Academy of Sciences
(Ann N Y Acad Sci)
Vol. 1202
Pg. 221-5
(Aug 2010)
ISSN: 1749-6632 [Electronic] United States |
PMID | 20712796
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Anti-Bacterial Agents
- Antimicrobial Cationic Peptides
- HAMP protein, human
- HFE protein, human
- Hamp protein, mouse
- Hemochromatosis Protein
- Hepcidins
- Histocompatibility Antigens Class I
- Membrane Proteins
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Topics |
- Anemia
(etiology, metabolism)
- Animals
- Anti-Bacterial Agents
(metabolism, therapeutic use)
- Antimicrobial Cationic Peptides
(genetics, metabolism, therapeutic use)
- Genetic Therapy
- Genetic Vectors
(genetics)
- Hemochromatosis Protein
- Hepcidins
- Histocompatibility Antigens Class I
(genetics, metabolism, therapeutic use)
- Humans
- Iron Overload
(etiology, metabolism, therapy)
- Membrane Proteins
(genetics, metabolism, therapeutic use)
- beta-Thalassemia
(complications, genetics, metabolism, therapy)
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