Hepatic hypoxia-inducible factor-2 down-regulates hepcidin expression in mice through an erythropoietin-mediated increase in erythropoiesis

Haematologica

Volumn 97, Issue 6, 2012, Pages 827-834

  Mastrogiannaki, Maria ^a,b,c   Matak, Pavle ^a,b,c   Mathieu, Jacques R R ^a,b,c   Delga, Stéphanie ^a,b,c   Mayeux, Patrick ^a,b,c   Vaulont, Sophie ^a,b,c   Peyssonnaux, Carole ^a,b,c  

^a INSERM   (France)

^b CNRS   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

Erythropoiesis; Hepatic HIF 2; Hepcidin expression

Indexed keywords

ERYTHROPOIETIN; ERYTHROPOIETIN ANTIBODY; HEMOGLOBIN; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR 2ALPHA; MESSENGER RNA;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; ENZYME LINKED IMMUNOSORBENT ASSAY; ERYTHROCYTE COUNT; ERYTHROPOIESIS; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION REGULATION; GENE REPRESSION; IRON ABSORPTION; IRON DEFICIENCY ANEMIA; IRON RESTRICTION; KNOCKOUT MOUSE; LIVER CELL; MALE; MOUSE; NONHUMAN; REAL TIME POLYMERASE CHAIN REACTION; RETICULOCYTE COUNT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANIMALS; ANTIBODIES, NEUTRALIZING; ANTIMICROBIAL CATIONIC PEPTIDES; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; ERYTHROPOIESIS; ERYTHROPOIETIN; FEMALE; FOOD, FORMULATED; GENE EXPRESSION REGULATION; HEPATOCYTES; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IRON; MALE; MICE; MICE, KNOCKOUT; PRIMARY CELL CULTURE; SIGNAL TRANSDUCTION; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84862148400     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2011.056119     Document Type: Article

References (40)

1. Weidemann A, Johnson RS. Nonrenal regulation of EPO synthesis. Kidney Int. 2009;75(7):682-8.
2. Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992;12(12):5447-54.
3. Semenza GL. Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis. Blood. 2009;114(10): 2015-9.
4. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122 (2-3):78-86.
5. Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science. 2008;320(5879):1088-92.
6. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008;8(6):502-11.
7. Silvestri L, Pagani A, Camaschella C. Furinmediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood. 2008;111(2):924-31.
8. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest. 2007; 117(7):1926-32.
9. Gordeuk VR, Miasnikova GY, Sergueeva AI, Niu X, Nouraie M, Okhotin DJ, et al. Chuvash polycythemia VHLR200W mutation is associated with downregulation of hepcidin expression. Blood. 2011;118:5278-82.
10. Lakhal S, Schodel J, Townsend AR, Pugh CW, Ratcliffe PJ, Mole DR. Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis. J Biol Chem. 2011;286(6): 4090-7.
11. Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, Peyssonnaux C. HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. J Clin Invest. 2009;119(5):1159-66.
12. Lee LG, Chen CH, Chiu LA. Thiazole orange: a new dye for reticulocyte analysis. Cytometry. 1986;7(6):508-17.
13. Ramey G, Deschemin JC, Vaulont S. Crosstalk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes. Haematologica. 2009;94(6):765-72.
14. He TC, Zhou S, da Costa LT, Yu J, Kinzler KW, Vogelstein B. A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci USA. 1998;95(5):2509-14.
15. Haase VH, Glickman JN, Socolovsky M, Jaenisch R. Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc Natl Acad Sci USA. 2001;98(4):1583-8.
16. Braliou GG, Verga Falzacappa MV, Chachami G, Casanovas G, Muckenthaler MU, Simos G. 2-Oxoglutarate-dependent oxygenases control hepcidin gene expression. J Hepatol. 2008;48(5):801-10.
17. Choi SO, Cho YS, Kim HL, Park JW. ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPalpha and STAT-3. Biochem Biophys Res Commun. 2007;356(1):312-7.
18. Volke M, Gale DP, Maegdefrau U, Schley G, Klanke B, Bosserhoff AK, et al. Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors. PLoS One. 2009;4(11):e7875.
19. McMahon S, Grondin F, McDonald PP, Richard DE, Dubois CM. Hypoxiaenhanced expression of the proprotein convertase furin is mediated by hypoxiainducible factor-1: impact on the bioactivation of proproteins. J Biol Chem. 2005;280 (8):6561-9.
20. Rankin EB, Biju MP, Liu Q, Unger TL, Rha J, Johnson RS, et al. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest. 2007;117(4):1068-77.
21. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110(7):1037-44.
22. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006;108(12):3730-5.
23. Vokurka M, Krijt J, Sulc K, Necas E. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res. 2006;55(6):667-74.
24. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica. 2010;95(3):505-8.
25. Kapitsinou PP, Liu Q, Unger TL, Rha J, Davidoff O, Keith B, et al. Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia. Blood. 2010;116 (16):3039-48.
26. Haase VH. Hypoxic regulation of erythropoiesis and iron metabolism. Am J Physiol Renal Physiol. 2010;299(1):F1-13.
27. Kautz L, Meynard D, Monnier A, Darnaud V, Bouvet R, Wang RH, et al. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood. 2008;112(4):1503-9.
28. Meynard D, Vaja V, Sun CC, Corradini E, Chen S, Lopez-Otin C, et al. Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood. 2011;118(3):747-56.
29. Ramos E, Kautz L, Rodriguez R, Hansen M, Gabayan V, Ginzburg Y, et al. Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice. Hepatology. 2011;53(4):1333-41.
30. Krijt J, Fujikura Y, Sefc L, Vokurka M, Hlobenova T, Necas E. Hepcidin downregulation by repeated bleeding is not mediated by soluble hemojuvelin. Physiol Res. 2010;59(1):53-9.
31. Pinto JP, Ribeiro S, Pontes H, Thowfeequ S, Tosh D, Carvalho F, et al. Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha. Blood. 2008;111(12): 5727-33.
32. Forejtnikova H, Vieillevoye M, Zermati Y, Lambert M, Pellegrino RM, Guihard S, et al. Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis. Blood. 2010;116(24):5357-67.
33. Nemeth E. Hepcidin in beta-thalassemia. Ann N Y Acad Sci. 2010;1202:31-5.
34. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13(9):1096-101.
35. Tanno T, Porayette P, Sripichai O, Noh SJ, Byrnes C, Bhupatiraju A, et al. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood. 2009;114(1):181-6.
36. Zhang AS, Anderson SA, Wang J, Yang F, DeMaster K, Ahmed R, et al. Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein. Blood. 2011;117(5):1687-99.
37. Chaston TB, Matak P, Pourvali K, Srai SK, McKie AT, Sharp PA. Hypoxia inhibits hepcidin expression in HuH7 hepatoma cells via decreased SMAD4 signaling. Am J Physiol Cell Physiol. 2011;300(4):C888-95.
38. Huang H, Constante M, Layoun A, Santos MM. Contribution of STAT3 and SMAD4 pathways to the regulation of hepcidin by opposing stimuli. Blood. 2009;113(15): 3593-9.
39. Leung PS, Srai SK, Mascarenhas M, Churchill LJ, Debnam ES. Increased duodenal iron uptake and transfer in a rat model of chronic hypoxia is accompanied by reduced hepcidin expression. Gut. 2005;54 (10):1391-5.
40. Piperno A, Galimberti S, Mariani R, Pelucchi S, Ravasi G, Lombardi C, et al. Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood. 2011;117(10):2953-9.