Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)

Journal of Clinical Investigation

Volumn 117, Issue 7, 2007, Pages 1926-1932

  Peyssonnaux, Carole ^a,b   Zinkernagel, Annelies S ^b   Schuepbach, Reto A ^c   Rankin, Erinn ^d   Vaulont, Sophie ^e,f   Haase, Volker H ^d   Nizet, Victor ^b   Johnson, Randall S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c SCRIPPS RESEARCH INSTITUTE   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e INSTITUT COCHIN   (France)

^f INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ERYTHROPOIETIN; FERROPORTIN 1; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON; VON HIPPEL LINDAU PROTEIN;

ANEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; ERYTHROPOIESIS; HOMEOSTASIS; HORMONE SYNTHESIS; HYPOXIA; IRON ABSORPTION; IRON METABOLISM; IRON OVERLOAD; MOLECULAR MECHANICS; MOUSE; NONHUMAN; OXYGEN TRANSPORT; PRIORITY JOURNAL; PROTEIN EXPRESSION; UPREGULATION; VON HIPPEL LINDAU DISEASE;

ALBUMINS; ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; BASE SEQUENCE; CATION TRANSPORT PROTEINS; DOWN-REGULATION; GENE DELETION; HEPATOCYTES; HOMEOSTASIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; INTEGRASES; IRON; LIVER; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; POLYCYTHEMIA; PROMOTER REGIONS (GENETICS); PROTEIN BINDING; UP-REGULATION; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 34447120059     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI31370     Document Type: Article

References (33)

1. Nemeth, E., et al. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 306:2090-2093.
2. Nicolas, G., et al. 2002. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. U. S. A. 99:4596-4601.
3. 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.
4. Lee, P., Peng, H., Gelbart, T., Wang, L., and Beutler, E. 2005. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc. Natl. Acad. Sci. U. S. A. 102:1906-1910.
5. 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.
6. Weinstein, D.A., et al. 2002. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood. 100:3776-3781.
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. Feder, J.N., et al. 1996. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 13:399-408.
9. Muckenthaler, M., et al. 2003. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat. Genet. 34:102-107.
10. Papanikolaou, G., et al. 2005. Hepcidin in iron overload disorders. Blood. 105:4103-4105.
11. Roetto, A., et al. 2003. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat. Genet. 33:21-22.
12. Semenza, G.L. 2001. HIF-1 and mechanisms of hypoxia sensing. Curr. Opin. Cell Biol. 13:167-171.
13. Flamme, I., et al. 1997. HRF, a putative basic helix-loop-helix-PAS- domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels. Mech. Dev. 63:51-60.
14. Ema, M., et al. 1997. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc. Natl. Acad. Sci. U. S. A. 94:4273-4278.
15. Tian, H., McKnight, S.L., and Russell, D.W. 1997. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 11:72-82.
16. Gu, Y.Z., Moran, S.M., Hogenesch, J.B., Wartman, L., and Bradfield, C.A. 1998. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr. 7:205-213.
17. Frazer, D.M., et al. 2002. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology. 123:835-844.
18. Kemna, E., Pickkers, P., Nemeth, E., van der Hoeven, H., and Swinkels, D. 2005. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 106:1864-1866.
19. Bhatia, S.N., Balis, U.J., Yarmush, M.L., and Toner, M. 1999. Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J. 13:1883-1900.
20. Rankin, E.B., et al. 2005. Inactivation of the arylhydrocarbon receptor nuclear translocator (Arnt) suppresses von Hippel-Lindau disease-associated vascular tumors in mice. Mol. Cell. Biol. 25:3163-3172.
21. Haase, V.H., Glickman, J.N., Socolovsky, M., and Jaenisch, R. 2001. Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc. Natl. Acad. Sci. U. S. A. 98:1583-1588.
22. Ang, S.O., et al. 2002. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat. Genet. 32:614-621.
23. Gordeuk, V.R., et al. 2004. Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. Blood. 103:3924-3932.
24. Wenger, R.H., and Gassmann, M. 1997. Oxygen(es) and the hypoxia-inducible factor-1. Biol. Chem. 378:609-616.
25. Abboud, S., and Haile, D.J. 2000. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275:19906-19912.
26. Viatte, L., et al. 2005. Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice. Blood. 105:4861-4864.
27. Huang, F.W., Pinkus, J.L., Pinkus, G.S., Fleming, M.D., and Andrews, N.C. 2005. A mouse model of juvenile hemochromatosis. J. Clin. Invest. 115:2187-2191. doi:10.1172/JCI25049.
28. Mazure, N.M., et al. 2002. Repression of alpha-fetoprotein gene expression under hypoxic conditions in human hepatoma cells: characterization of a negative hypoxia response element that mediates opposite effects of hypoxia inducible factor-1 and c-Myc. Cancer Res. 62:1158-1165.
29. Chen, K.F., Lai, Y.Y., Sun, H.S., and Tsai, S.J. 2005. Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha. Nucleic Acids Res. 33:5190-5198.
30. Yoon, D., et al. 2006. Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J. Biol. Chem. 281:25703-25711.
31. Brugnara, C., et al. 1994. Effects of subcutaneous recombinant human erythropoietin in normal subjects: development of decreased reticulocyte hemoglobin content and iron-deficient erythropoiesis. J. Lab. Clin. Med. 123:660-667.
32. Finch, C. 1994. Regulators of iron balance in humans. Blood. 84:1697-1702.
33. Torrance, J.D., Charlton, R.W., Schmaman, A., Lynch, S.R., and Bothwell, T.H. 1968. Storage iron in "muscle". J. Clin. Pathol. 21:495-500.