Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 291, Issue 2, 2006, Pages

  Constante, Marco ^a   Jiang, Wenlei ^a   Wang, Dongmei ^a   Raymond, Valérie Ann ^b   Bilodeau, Marc ^a,b   Santos, Manuela M ^a  

^a NOTRE DAME HOSPITAL   (Canada)

^b UNIVERSITY OF MONTREAL   (Canada)

Author keywords

2m; Ferroportin 1; Hereditary hemochromatosis; Lipopolysaccharide; Toll like receptor 4

Indexed keywords

FERROPORTIN 1; HEPCIDIN; HFE PROTEIN; IRON; TOLL LIKE RECEPTOR 4;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BASEMENT MEMBRANE; CONTROLLED STUDY; GENETIC ANALYSIS; HOMEOSTASIS; INFLAMMATION; IRON METABOLISM; IRON OVERLOAD; IRON RESTRICTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; CELLS, CULTURED; HISTOCOMPATIBILITY ANTIGENS CLASS I; INFLAMMATION; IRON; IRON OVERLOAD; LIVER; MEMBRANE PROTEINS; MICE; MICE, INBRED C3H; MICE, KNOCKOUT; SPLEEN;

EID: 33745767741     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00092.2006     Document Type: Article

References (49)

1. Abboud S and Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 275: 19906-19912, 2000.
2. Ahmad KA, Ahmann JR, Migas MC, Waheed A, Britton RS, Bacon BR, Sly WS, and Fleming RE. Decreased liver hepcidin expression in the hfe knockout mouse. Blood Cells Mol Dis 29: 361-366, 2002.
3. Aisen P, Wessling-Resnick M, and Leibold EA. Iron metabolism. Curr Opin Chem Biol 3: 200-206, 1999.
4. Ajioka RS, Levy JE, Andrews NC, and Kushner JP. Regulation of iron absorption in Hfe mutant mice. Blood 100: 1465-1469, 2002.
5. Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DH, Subramaniam VN, Powell LW, Anderson GJ, and Ramm GA. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361: 669-673, 2003.
6. Cardoso EM, Macedo MG, Rohrlich P, Ribeiro E, Silva MT, Lemonnier FA, and de Sousa M. Increased hepatic iron in mice lacking classical MHC class I molecules. Blood 100: 4239-4241, 2002.
7. Chen H, Su T, Attieh ZK, Fox TC, McKie AT, Anderson GJ, and Vulpe CD. Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency. Blood 102: 1893-1899, 2003.
8. Courselaud B, Troadec MB, Fruchon S, Ilyin G, Borot N, Leroyer P, Coppin H, Brissot P, Roth MP, and Loreal O. Strain and gender modulate hepatic hepcidin 1 and 2 mRNA expression in mice. Blood Cells Mol Dis 32: 283-289, 2004.
9. Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, and Andrews NC. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 1: 191-200, 2005.
10. Dupic F, Fruchon S, Bensaid M, Borot N, Radosavljevic M, Loreal O, Brissot P, Gilfillan S, Bahram S, Coppin H, and Roth MP. Inactivation of the hemochromatosis gene differentially regulates duodenal expression of iron-related mRNAs between mouse strains. Gastroenterology 122: 745-751, 2002.
11. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, and Wolff RK. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13: 399-408, 1996.
12. Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, Prass CE, Starnes SM, Wolff RK, Parkkila S, Sly WS, and Schatzman RC. The hemochromatosis founder mutation in HLA-H disrupts beta 2-microglobulin interaction and cell surface expression. J Biol Chem 272: 14025-14028, 1997.
13. Fleming RE, Holden CC, Tomatsu S, Waheed A, Brunt EM, Britton RS, Bacon BR, Roopenian DC, and Sly WS. Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis. Proc Natl Acad Sci USA 98: 2707-2711, 2001.
14. Frazer D, Wilkins S, Becker E, Vulpe C, McKie A, Trinder D, and Anderson G. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 123: 835-844, 2002.
15. Frazer DM, Wilkins SJ, Millard KN, McKie AT, Vulpe CD, and Anderson GJ. Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE. Br J Haematol 126: 434-436, 2004.
16. Hentze MW, Muckenthaler MU, and Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell 117: 285-297, 2004.
17. Herrmann T, Muckenthaler M, van der Hoeven F, Brennan K, Gehrke SG, Hubert N, Sergi C, Grone HJ, Kaiser I, Gosch I, Volkmann M, Riedel HD, Hentze MW, Stewart AF, and Stremmel W. Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin. J Mol Med 82: 39-48, 2004.
18. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, and Akira S. Cutting edge: Toll-like receptor 4 (TLR-4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR-4 as the Lps gene product. J Immunol 162: 3749-3752, 1999.
19. Knutson MD, Vafa MR, Haile DJ, and Wessling-Resnick M. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood 102: 4191-4197, 2003.
20. Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, and Adermann K. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 480: 147-150, 2000.
21. Laftah AH, Ramesh B, Simpson RJ, Solanky N, Bahram S, Schumann K, Debnam ES, and Srai SKS. Effect of hepcidin on intestinal iron absorption in mice. Blood 103: 3940-3944, 2004.
22. Laftah AH, Simpson RJ, Beaumont N, Bahram S, Schumann K, and Srai SK. Hypoxic response of iron absorption is not affected by the Hfe gene knock-out in mice. Br J Haematol 123: 170-172, 2003.
23. Lee P, Peng H, Gelbart T, and Beutler E. The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes. Proc Natl Acad Sci USA 101: 9263-9265, 2004.
24. Levy JE, Montross LK, and Andrews NC. Genes that modify the hemochromatosis phenotype in mice. J Clin Invest 105: 1209-1216, 2000.
25. Levy JE, Montross LK, Cohen DE, Fleming MD, and Andrews NC. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 94: 9-11, 1999.
26. Liu Xb Hill P and Haile DJ. Role of the ferroportin iron-responsive element in iron and nitric oxide dependent gene regulation. Blood Cells Mol Dis 29: 315-326, 2002.
27. Lymboussaki A, Pignatti E, Montosi G, Garuti C, Haile DJ, and Pietrangelo A. The role of the iron responsive element in the control of ferroportin1/IREG1/MTP1 gene expression. J Hepatol 39: 710-715, 2003.
28. Makui H, Soares RJ, Jiang W, Constante M, and Santos MM. Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading. Blood 106: 2189-2195, 2005.
29. McLaren GD, Nathanson MH, Jacobs A, Trevett D, and Thomson W. Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis. J Lab Clin Med 117: 390-401, 1991.
30. Miranda CJ, Makui H, Andrews NC, and Santos MM. Contributions of beta2-microglobulin-dependent molecules and lymphocytes to iron regulation: insights from HfeRag1(-/-) and β2mRag1(-/-) double knock-out mice. Blood 103: 2847-2849, 2004.
31. Muckenthaler M, Roy CN, Custodio AO, Minana B, deGraaf J, Montross LK, Andrews NC, and Hentze MW. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat Genet 34: 102-107, 2003.
32. Muckenthaler MU, Rodrigues P, Macedo MG, Minana B, Brennan K, Cardoso EM, Hentze MW, and de Sousa M. Molecular analysis of iron overload in [beta]2-microglobulin-deficient mice. Blood Cells Mol Dis 33: 125-131, 2004.
33. Mukhopadhyay S, Herre J, Brown GD, and Gordon S. The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology 112: 521-530, 2004.
34. Musallam L, Ethier C, Haddad PS, and Bilodeau M. Role of EGF receptor tyrosine kinase activity in antiapoptotic effect of EGF on mouse hepatocytes. Am J Physiol Gastrointest Liver Physiol 280: G1360-G1369, 2001.
35. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, and Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306: 2090-2093, 2004.
36. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, and Vaulont S. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98: 8780-8785, 2001.
37. Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, and Vaulont S. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 99: 4596-4601, 2002.
38. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, and Vaulont S. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110: 1037-1044, 2002.
39. Niederkofler V, Salie R, and Arber S. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest 115: 2180-2186, 2005.
40. Park CH, Valore EV, Waring AJ, and Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276: 7806-7810, 2001.
41. Pietrangelo A. Hereditary hemochromatosis-a new look at an old disease. N Engl J Med 350: 2383-2397, 2004.
42. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, and Loreal O. 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, 2001.
43. Roy CN, Custodio AO, de Graaf J, Schneider S, Akpan I, Montross LK, Sanchez M, Gaudino A, Hentze MW, Andrews NC, and Muckenthaler MU. An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide- induced inflammation in mice. Nat Genet 36: 481-485, 2004.
44. Santos M, Clevers H, de Sousa M, and Marx JJ. Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice. Blood 91: 3059-3065, 1998.
45. Santos M, Schilham MW, Rademakers LH, Marx JJ, de Sousa M, and Clevers H. Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man. J Exp Med 184: 1975-1985, 1996.
46. Spivak JL. The anaemia of cancer: death by a thousand cuts. Nature Rev Cancer 5: 543-555, 2005.
47. Viatte L, Lesbordes-Brion JC, Lou DQ, Bennoun M, Nicolas G, Kahn A, Canonne-Hergaux F, and Vaulont S. Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice. Blood 105: 4861-4864, 2005.
48. Yeh Ky Yeh M and Glass J. Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat. Am J Physiol Gastrointest Liver Physiol 286: G385-G394, 2004.
49. Zhou XY, Tomatsu S, Fleming RE, Parkkila S, Waheed A, Jiang J, Fei Y, Brunt EM, Ruddy DA, Prass CE, Schatzman RC, O'Neill R, Britton RS, Bacon BR, and Sly WS. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci USA 95: 2492-2497, 1998.