Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function

Blood - Tập 106 - Trang 746-748 - 2005
Lénaïck Détivaud, Elizabeta Nemeth, Karim Boudjema, Bruno Turlin, Marie-Bérengère Troadec, Patricia Leroyer, Martine Ropert, Sylvie Jacquelinet, Brice Courselaud, Tomas Ganz, Pierre Brissot, Olivier Loréal

Tóm tắt

Abstract

Hepcidin, a key regulator of iron metabolism, is synthesized by the liver. Hepcidin binds to the iron exporter ferroportin to regulate the release of iron into plasma from macrophages, hepatocytes, and enterocytes. We analyzed liver samples from patients undergoing hepatic surgery for cancer or receiving liver transplants and analyzed correlations between clinical parameters and liver hepcidin mRNA and urinary hepcidin concentrations. Despite the many potential confounding influences, urinary hepcidin concentrations significantly correlated with hepatic hepcidin mRNA concentrations, indicating that hepcidin quantification in urine is a valid approach to evaluate hepcidin expression. Moreover, we found in humans that hepcidin levels correlated with hepatic iron stores and hemoglobin levels and may also be affected by hepatic dysfunction. (Blood. 2005;106:746-748)


Tài liệu tham khảo

Krause A, Neitz S, Magert HJ, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett.2000;480: 147-150. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem.2001;276: 7806-7810. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem.2001;276: 7811-7819. Nicolas G, Chauvet C, Viatte L, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest.2002;110: 1037-1044. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acutephase protein. Blood.2003;101: 2461-2463. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest.2004;113: 1271-1276. Courselaud B, Pigeon C, Inoue Y, et al. C/EBP alpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism. J Biol Chem.2002;277: 41163-41170. Courselaud B, Troadec MB, Fruchon S, et al. Strain and gender modulate hepatic hepcidin 1 and 2 mRNA expression in mice. Blood Cells Mol Dis.2004;32: 283-289. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A.2001;98: 8780-8785. Nicolas G, Bennoun M, Porteu A, et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci U S A.2002;99: 4596-4601. Roetto A, Papanikolaou G, Politou M, et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet.2003;33: 21-22. Bridle KR, Frazer DM, Wilkins SJ, et al. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet.2003;361: 669-673. Gehrke SG, Kulaksiz H, Herrmann T, et al. Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to serum transferrin saturation and non-transferrin-bound iron. Blood.2003;102: 371-376. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood.2002;100: 3776-3781. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates iron efflux by binding to ferroportin and inducing its internalization. Science.2004;279: 51739-51744. Ahmad KA, Ahmann JR, Migas MC, et al. Decreased liver hepcidin expression in the Hfe knockout mouse. Blood Cells Mol Dis.2002;29: 361-366. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology.1996;24: 289-293. Barry M, Sherlock S. Measurement of liver-iron concentration in needle biopsy specimens. Lancet.1971;2: 100-103.