Hepcidin and Hfe in iron overload in β-thalassemia

• Published in: Annals of the New York Academy of Sciences 2010-08, Vol.1202 (1), p.221-225
• Main Authors: Gardenghi, Sara, Ramos, Pedro, Follenzi, Antonia, Rao, Niva, Rachmilewitz, Eliezer A., Giardina, Patricia J., Grady, Robert W., Rivella, Stefano
• Format: Article
• Language: English
• Subjects: 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; beta-Thalassemia - complications; beta-Thalassemia - genetics; beta-Thalassemia - metabolism; beta-Thalassemia - therapy; Genetic Therapy; Genetic Vectors - genetics; Hemochromatosis Protein; hepcidin; Hepcidins; Hfe; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class I - therapeutic use; Humans; iron overload; Iron Overload - etiology; Iron Overload - metabolism; Iron Overload - therapy; lentiviral vectors; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Proteins - therapeutic use; β-thalassemia
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2010.05595.x

Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with β‐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 β‐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 β‐thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.