Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron.

Abstract

Experimental data suggest the antimicrobial peptide hepcidin as a central regulator in iron homeostasis. In this study, we characterized the expression of human hepcidin in experimental and clinical iron overload conditions, including hereditary hemochromatosis. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we determined expression of hepcidin and the most relevant iron-related genes in liver biopsies from patients with hemochromatosis and iron-stain-negative control subjects. Regulation of hepcidin mRNA expression in response to transferrin-bound iron, non-transferrin-bound iron, and deferoxamine was analyzed in HepG2 cells. Hepcidin expression correlated significantly with serum ferritin levels in controls, whereas no significant up-regulation was observed in patients with hemochromatosis despite iron-overload conditions and high serum ferritin levels. However, patients with hemochromatosis showed an inverse correlation between hepcidin transcript levels and the serum transferrin saturation. Moreover, we found a significant correlation between hepatic transcript levels of hepcidin and transferrin receptor-2 irrespective of the iron status. In vitro data indicated that hepcidin expression is down-regulated in response to non-transferrin-bound iron. In conclusion, the presented data suggest a close relationship between the transferrin saturation and hepatic hepcidin expression in hereditary hemochromatosis. Although the causality is not yet clear, this interaction might result from a down-regulation of hepcidin expression in response to significant levels of non-transferrin-bound iron.

• Authors: Sven G Gehrke, Hasan Kulaksiz, Thomas Herrmann, Hans-Dieter Riedel, Karin Bents, Claudia Veltkamp, Wolfgang Stremmel
• Journal: Blood (Blood) Vol. 102 Issue 1 Pg. 371-6 (Jul 01 2003) ISSN: 0006-4971 [Print] United States
• PMID: 12637325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimicrobial Cationic Peptides
• HAMP protein, human
• Hepcidins
• Receptors, Transferrin
• Transferrin
• RNA
• Iron

Topics

• Antimicrobial Cationic Peptides (analysis, biosynthesis, genetics)
• Case-Control Studies
• Family Health
• Gene Expression Regulation
• Hemochromatosis (metabolism, pathology)
• Hepcidins
• Humans
• Iron (blood)
• Liver (pathology)
• RNA (analysis)
• Receptors, Transferrin (analysis, genetics)
• Transferrin (metabolism)
• Tumor Cells, Cultured