Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload

Journal of Clinical Investigation

Volumn 115, Issue 8, 2005, Pages 2180-2186

  Niederkofler, Vera ^a   Salie, Rishard ^a   Arber, Silvia ^a,b  

^a UNIVERSITY OF BASEL   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

FERROPORTIN 1; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; GLYPICAN; HEMOJUVELIN; HEPCIDIN; IRON BINDING PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; GENE; GENE MUTATION; HJV GENE; HOMEOSTASIS; INFLAMMATION; IRON ABSORPTION; IRON OVERLOAD; IRON STORAGE; LIVER; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS;

ANIMALS; CYTOKINES; GENE EXPRESSION REGULATION; HEMOCHROMATOSIS; HEPATOCYTES; HUMANS; INFLAMMATION; IRON OVERLOAD; IRON, DIETARY; MEMBRANE PROTEINS; MICE; MICE, MUTANT STRAINS; SIGNAL TRANSDUCTION;

EID: 23644444316     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI25683     Document Type: Article

References (35)

1. Hentze, M.W., Muckenthaler, M.U., and Andrews, N.C. 2004. Balancing acts: molecular control of mammalian iron metabolism [review]. Cell. 117:285-297.
2. Andrews, N.C. 2005. Molecular control of iron metabolism. Best. Pract. Res. Clin. Haematol. 18:159-169.
3. Nemeth, E., et al. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 306:2090-2093.
4. Nemeth, E., et al. 2004. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 113:1271-1276. doi:10.1172/JCI200420945.
5. Lee, P., Peng, H., Gelbart, T., and Beutler, E. 2004. The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes. Proc. Natl. Acad. Sci. U. S. A. 101:9263-9265.
6. Krijt, J., Vokurka, M., Chang, K.T., and Necas, E. 2004. Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin. Blood. 104:4308-4310.
7. Nicolas, G., et al. 2002. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 110:1037-1044. doi:10.1172/JCI200215686.
8. Pigeon, C., et al. 2001. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J. Biol. Chem. 276:7811-7819.
9. Luft, F.C. 2004. Hepcidin comes to the rescue. J. Mol. Med. 82:345-347.
10. Pietrangelo, A. 2004. Hereditary hemochromatosis-a new look at an old disease [review]. N. Engl. J. Med. 350:2383-2397.
11. Beutler, E., Hoffbrand, A.V., and Cook, J.D. 2003. Iron deficiency and overload [review]. Hematology. (Am. Soc. Hematol. Educ. Program.). 2003:40-61.
12. Brissot, P., Troadec, M.B., and Loreal, O. 2004. The clinical relevance of new insights in iron transport and metabolism. Curr. Hematol. Rep. 3:107-115.
13. Papanikolaou, G., et al. 2004. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat. Genet. 36:77-82.
14. Niedetkofler, V., Salie, R., Sigrist, M., and Arber, S. 2004. Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J. Neurosci. 24:808-818.
15. Monnier, P.P., et al. 2002. RGM is a repulsive guidance molecule for retinal axons. Nature. 419:392-395.
16. Samad, T.A., et al. 2004. DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J. Neurosci. 24:2027-2036.
17. Guidotti, J.E., et al. 2003. Liver cell polyploidization: a pivotal role for binuclear hepatocytes. J. Biol. Chem. 278:19095-19101.
18. Seglen, P.O. 1997. DNA ploidy and autophagic protein degradation as determinants of hepatocellular growth and survival. Cell Biol. Toxicol. 13:301-315.
19. Parviz, F., et al. 2003. Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat. Genet. 34:292-296,
20. Benten, D., et al. 2005. Hepatic targeting of transplanted liver sinusoidal endothelial cells in intact mice. Hepatology. doi:10.1002/hep.20746.
21. Kawabata, H., et al. 2005. Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood. 105:376-381.
22. Fleming, R.E., et al. 2001. Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis. Proc. Natl. Acad. Sci. U. S. A. 98:2707-2711.
23. Zhou, X.Y., et al. 1998. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc. Natl. Acad. Sci. U. S. A. 95:2492-2497.
24. Nicolas, G., et al. 2001. 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. 98:8780-8785.
25. Andrews, N.C. 2004. Anemia of inflammation: the cytokine-hepcidin link. J. Clin. Invest. 113:1251-1253. doi:10.1172/JCI200421441.
26. Courselaud, B., et al. 2002. C/EBPalpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Crosstalk between C/EBP pathway and iron metabolism. J. Biol. Chem. 277:41163-41170.
27. Zetterstrom, M., Sundgren-Andersson, A.K., Ostlund, P., and Bartfai, T. 1998. Delineation of the proinflammatory cytokine cascade in fever induction. Ann. N. Y. Acad. Sci. 856:48-52.
28. Yeh, K.Y., Yeh, M., and Glass, J. 2004. Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat. Am. J. Physiol. Gastrointest. Liver Physiol. 286:G385-G394.
29. Chorney, M.J., Yoshida, Y., Meyer, P.N., Yoshida, M., and Gerhard, G.S. 2003. The enigmatic role of the hemochromatosis protein (HFE) in iron absorption. Trends Mol. Med. 9:118-125.
30. Zhang, A.S., Xiong, S., Tsukamoto, H., and Enns, C.A. 2004. Localization of iron metabolism-related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes. Blood. 103:1509-1514.
31. Kawabata, H., et al. 2001. Regulation of expression of murine transferrin receptor 2. Blood. 98:1949-1954.
32. Arber, S., et al. 1997, MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell. 88:393-403.
33. Gottshall, K.R., et al. 1997. Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 94:4710-4715.
34. Arber, S., et al. 1999. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 23:659-674.
35. Torrance, J.D., and Bothwell, T.H. 1980. Tissue iron stores. In Methods in hematology. Volume 1. J.D. Cook, editor. Churchill Livingstone Press. New York, New York, USA. 90-115.