title: Hepcidin and Hfe in iron overload in beta-thalassemia.
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.
authors: Division of Hematology-Oncology, Department of Pediatrics, Children's Cancer and Blood Foundation Laboratories, Weill Cornell Medical College, New York, New York, USA.
authors: Sara
authors: S
authors: Gardenghi
authors: Pedro
authors: P
authors: Ramos
authors: Antonia
authors: A
authors: Follenzi
authors: Niva
authors: N
authors: Rao
authors: Eliezer A
authors: EA
authors: Rachmilewitz
authors: Patricia J
authors: PJ
authors: Giardina
authors: Robert W
authors: RW
authors: Grady
authors: Stefano
authors: S
authors: Rivella
mesh_terms: D000740:Anemia / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D019190:Iron Overload / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C103673:HFE protein, human; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins