Hepcidin and Hfe in iron overload in beta-thalassemia

Ann N Y Acad Sci. 2010 Aug;1202:221-5. doi: 10.1111/j.1749-6632.2010.05595.x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia / etiology
  • Anemia / metabolism
  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / therapeutic use
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Genetic Therapy
  • Genetic Vectors / genetics
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Antigens Class I / therapeutic use
  • Humans
  • Iron Overload / etiology
  • Iron Overload / metabolism*
  • Iron Overload / therapy
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / therapeutic use
  • beta-Thalassemia / complications
  • beta-Thalassemia / genetics
  • beta-Thalassemia / metabolism*
  • beta-Thalassemia / therapy

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • HFE protein, human
  • Hamp protein, mouse
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Membrane Proteins