Regulation of Hepcidin by Erythropoiesis: The Story So Far

Literature Cited

1. Altamura S, Kessler R, Gröne HJ, Gretz N, Hentze MW. 1.  et al. 2014. Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload. Cell Metab. 20:359–67 [Google Scholar]
2. Anderson ER, Taylor M, Xue X, Ramakrishnan SK, Martin A. 2.  et al. 2013. Intestinal HIF2α promotes tissue-iron accumulation in disorders of iron overload with anemia. PNAS 110:E4922–30 [Google Scholar]
3. Andrews NC. 3.  1999. Disorders of iron metabolism. N. Engl. J. Med. 341:1986–95 [Google Scholar]
4. Andriopoulos B Jr., Corradini E, Xia Y, Faasse SA, Chen S. 4.  et al. 2009. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat. Genet. 41:482–87 [Google Scholar]
5. Armitage AE, Eddowes LA, Gileadi U, Cole S, Spottiswoode N. 5.  et al. 2011. Hepcidin regulation by innate immune and infectious stimuli. Blood 118:4129–39 [Google Scholar]
6. Arnold K, Bordoli L, Kopp J, Schwede T. 6.  2006. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22:195–201 [Google Scholar]
7. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND. 7.  et al. 2010. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 95:505–8 [Google Scholar]
8. Babitt JL, Lin HY. 8.  2011. The molecular pathogenesis of hereditary hemochromatosis. Semin. Liv. Dis. 31:280–92 [Google Scholar]
9. Bardou-Jacquet E, Ben Ali Z, Beaumont-Epinette MP, Loreal O, Jouanolle AM, Brissot P. 9.  2014. Non-HFE hemochromatosis: pathophysiological and diagnostic aspects. Clin. Res. Hepatol. Gastroenterol. 38:143–54 [Google Scholar]
10. Benkert P, Tosatto SC, Schomburg D. 10.  2008. QMEAN: a comprehensive scoring function for model quality assessment. Proteins 71:261–77 [Google Scholar]
11. Besson-Fournier C, Latour C, Kautz L, Bertrand J, Ganz T. 11.  et al. 2012. Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling. Blood 120:431–39 [Google Scholar]
12. Boudko SP, Sasaki T, Engel J, Lerch TF, Nix J. 12.  et al. 2009. Crystal structure of human collagen XVIII trimerization domain: a novel collagen trimerization Fold. J. Mol. Biol. 392:787–802 [Google Scholar]
13. Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I. 13.  et al. 2008. Severe anemia in Malawian children. N. Engl. J. Med. 358:888–99 [Google Scholar]
14. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. 14.  2014. Guidelines for the Management of Transfusion Dependent Thalassaemia Cyprus: Thalass. Int. Fed.
15. Casals-Pascual C, Huang H, Lakhal-Littleton S, Thezenas ML, Kai O. 15.  et al. 2012. Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria. Haematologica 97:1695–98 [Google Scholar]
16. Casals-Pascual C, Kai O, Cheung JO, Williams S, Lowe B. 16.  et al. 2006. Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo. Blood 108:2569–77 [Google Scholar]
17. Casanovas G, Swinkels DW, Altamura S, Schwarz K, Laarakkers CM. 17.  et al. 2011. Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II. J. Mol. Med. 89:811–16 [Google Scholar]
18. Casanovas G, Vujic Spasic M, Casu C, Rivella S, Strelau J. 18.  et al. 2012. The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice. Haematologica 98:444–47 [Google Scholar]
19. Chaston TB, Matak P, Pourvali K, Srai SK, McKie AT, Sharp PA. 19.  2011. Hypoxia inhibits hepcidin expression in HuH7 hepatoma cells via decreased SMAD4 signaling. Am. J. Physiol. Cell Physiol. 300:C888–95 [Google Scholar]
20. Díaz V, Gammella E, Recalcati S, Santambrogio P, Naldi AM. 20.  et al. 2013. Liver iron modulates hepcidin expression during chronically elevated erythropoiesis in mice. Hepatology 58:2122–32 [Google Scholar]
21. Drakesmith H, Schimanski LM, Ormerod E, Merryweather-Clarke AT, Viprakasit V. 21.  et al. 2005. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 106:1092–97 [Google Scholar]
22. Eck MJ, Sprang SR. 22.  1989. The structure of tumor necrosis factor-alpha at 2.6 Å resolution. Implications for receptor binding. J. Biol. Chem. 264:17595–605 [Google Scholar]
23. Erlandson ME, Walden B, Stern G, Hilgartner MW, Wehman J, Smith CH. 23.  1962. Studies on congenital hemolytic syndromes, IV. Gastrointestinal absorption of iron. Blood 19:359–78 [Google Scholar]
24. Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA. 24.  et al. 2008. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat. Genet. 40:569–71 [Google Scholar]
25. Finberg KE, Whittlesey RL, Fleming MD, Andrews NC. 25.  2010. Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis. Blood 115:3817–26 [Google Scholar]
26. Finch C. 26.  1994. Regulators of iron balance in humans. Blood 84:1697–702 [Google Scholar]
27. Folgueras AR, de Lara FM, Pendás AM, Garabaya C, Rodríguez F. 27.  et al. 2008. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood 112:2539–45 [Google Scholar]
28. Frazer DM, Wilkins SJ, Darshan D, Badrick AC, McLaren GD, Anderson GJ. 28.  2012. Stimulated erythropoiesis with secondary iron loading leads to a decrease in hepcidin despite an increase in bone morphogenetic protein 6 expression. Br. J. Haematol. 157:615–26 [Google Scholar]
29. Ganz T. 29.  2011. Hepcidin and iron regulation, 10 years later. Blood 117:4425–33 [Google Scholar]
30. Ganz T. 30.  2013. Systemic iron homeostasis. Physiol. Rev. 93:1721–41 [Google Scholar]
31. Ganz T, Nemeth E. 31.  2012. Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb. Perspect. Med. 2:a011668 [Google Scholar]
32. Gardenghi S, Grady RW, Rivella S. 32.  2010. Anemia, ineffective erythropoiesis, and hepcidin: interacting factors in abnormal iron metabolism leading to iron overload in β-thalassemia. Hematol. Oncol. Clin. North Am. 24:1089–107 [Google Scholar]
33. Gardenghi S, Renaud TM, Meloni A, Casu C, Crielaard BJ. 33.  et al. 2014. Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus. Blood 123:1137–45 [Google Scholar]
34. Gordeuk VR, Miasnikova GY, Sergueeva AI, Niu X, Nouraie M. 34.  et al. 2011. Chuvash polycythemia VHLR200W mutation is associated with down-regulation of hepcidin expression. Blood 118:5278–82 [Google Scholar]
35. Guida C, Altamura S, Klein FA, Galy B, Boutros M. 35.  et al. 2015. A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia. Blood 125:2265–75 [Google Scholar]
36. Jones E, Pasricha SR, Allen A, Evans P, Fisher CA. 36.  et al. 2015. Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait. Blood 125:873–80 [Google Scholar]
37. Jonker FAM, Calis JCJ, Phiri K, Kraaijenhagen RJ, Brabin BJ. 37.  et al. 2013. Low hepcidin levels in severely anemic Malawian children with high incidence of infectious diseases and bone marrow iron deficiency. PLOS ONE 8:e78964 [Google Scholar]
38. Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A. 38.  et al. 2006. The effects of erythropoietic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica 91:809–12 [Google Scholar]
39. Kautz L, Jung G, Du X, Gabayan V, Chapman J. 39.  et al. 2015. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia. Blood 126:2031–37 [Google Scholar]
40. Kautz L, Jung G, Nemeth E, Ganz T. 40.  2014. Erythroferrone contributes to recovery from anemia of inflammation. Blood 124:2569–74 [Google Scholar]
41. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. 41.  2014. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat. Genet. 46:678–84 [Google Scholar]
42. Kautz L, Meynard D, Monnier A, Darnaud V, Bouvet R. 42.  et al. 2008. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 112:1503–9 [Google Scholar]
43. Kautz L, Nemeth E. 43.  2014. Molecular liaisons between erythropoiesis and iron metabolism. Blood 124:479–82 [Google Scholar]
44. Kearney SL, Nemeth E, Neufeld EJ, Thapa D, Ganz T. 44.  et al. 2007. Urinary hepcidin in congenital chronic anemias. Pediatr. Blood Cancer 48:57–63 [Google Scholar]
45. Kim A, Nemeth E. 45.  2015. New insights into iron regulation and erythropoiesis. Curr. Opin. Hematol. 22:199–205 [Google Scholar]
46. Lakhal S, Schödel J, Townsend ARM, Pugh CW, Ratcliffe PJ, Mole DR. 46.  2011. Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis. J. Biol. Chem. 286:4090–97 [Google Scholar]
47. Lesbordes-Brion JC, Viatte L, Bennoun M, Lou DQ, Ramey G. 47.  et al. 2006. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood 108:1402–5 [Google Scholar]
48. Liu Q, Davidoff O, Niss K, Haase VH. 48.  2012. Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis. J. Clin. Investig. 122:4635–44 [Google Scholar]
49. Mastrogiannaki M, Matak P, Mathieu JRR, Delga S, Mayeux P. 49.  et al. 2012. Hepatic hypoxia-inducible factor-2 down-regulates hepcidin expression in mice through an erythropoietin-mediated increase in erythropoiesis. Haematologica 97:827–34 [Google Scholar]
50. Merryweather-Clarke AT, Atzberger A, Soneji S, Gray N, Clark K. 50.  et al. 2011. Global gene expression analysis of human erythroid progenitors. Blood 117:e96–108 [Google Scholar]
51. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. 51.  2009. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat. Genet. 41:478–81 [Google Scholar]
52. Min X, Lemon B, Tang J, Liu Q, Zhang R. 52.  et al. 2012. Crystal structure of a single-chain trimer of human adiponectin globular domain. FEBS Lett. 586:912–17 [Google Scholar]
53. Nai A, Pellegrino RM, Rausa M, Pagani A, Boero M. 53.  et al. 2014. The erythroid function of transferrin receptor 2 revealed by Tmprss6 inactivation in different models of transferrin receptor 2 knockout mice. Haematologica 99:1016–21 [Google Scholar]
54. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S. 54.  et al. 2004. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Investig. 113:1271–76 [Google Scholar]
55. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A. 55.  et al. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–93 [Google Scholar]
56. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. 56.  2003. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 101:2461–63 [Google Scholar]
57. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. 57.  2006. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 108:3730–35 [Google Scholar]
58. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL. 58.  et al. 2004. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat. Genet. 36:77–82 [Google Scholar]
59. Parrow NL, Fleming RE. 59.  2014. Bone morphogenetic proteins as regulators of iron metabolism. Annu. Rev. Nutr. 34:77–94 [Google Scholar]
60. Pasricha SR, Atkinson SH, Armitage AE, Khandwala S, Veenemans J. 60.  et al. 2014. Expression of the iron hormone hepcidin distinguishes different types of anemia in African children. Sci. Transl. Med. 6:235re3 [Google Scholar]
61. Pasricha SR, Frazer DM, Bowden DK, Anderson GJ. 61.  2013. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with β-thalassemia major: a longitudinal study. Blood 122:124–33 [Google Scholar]
62. Pasricha SR, McQuilten Z, Westerman M, Keller A, Nemeth E. 62.  et al. 2011. Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors. Haematologica 96:1099–105 [Google Scholar]
63. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S. 63.  et al. 2007. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J. Clin. Investig. 117:1926–32 [Google Scholar]
64. Pietrangelo A. 64.  2004. The ferroportin disease. Blood Cells Mol. Dis. 32:131–38 [Google Scholar]
65. Pinto JP, Ribeiro S, Pontes H, Thowfeequ S, Tosh D. 65.  et al. 2008. Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPα. Blood 111:5727–33 [Google Scholar]
66. Piperno A, Galimberti S, Mariani R, Pelucchi S, Ravasi G. 66.  et al. 2011. Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood 117:2953–59 [Google Scholar]
67. Porter JB. 67.  2009. Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease. Hemoglobin 33:S37–45 [Google Scholar]
68. Porter JB, Garbowski M. 68.  2014. The pathophysiology of transfusional iron overload. Hematol. Oncol. Clin. North Am. 28:683–701 [Google Scholar]
69. Pospíilová D, Houda J, Holub D, Ludíková B, Mojzíková R. 69.  et al. 2012. Significance of hepcidin level assessment in the diagnosis of selected types of anaemia in childhood. Transfuze Hematol. Dnes. 18:58–65 [Google Scholar]
70. Premawardhena A, Fisher CA, Olivieri NF, de Silva S, Arambepola M. 70.  et al. 2005. Haemoglobin E beta thalassaemia in Sri Lanka. Lancet 366:1467–70 [Google Scholar]
71. Prentice AM, Doherty CP, Abrams SA, Cox SE, Atkinson SH. 71.  et al. 2012. Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood 119:1922–28 [Google Scholar]
72. Rees DC, Styles L, Vichinsky EP, Clegg JB, Weatherall DJ. 72.  1998. The hemoglobin E syndromes. Ann. N. Y. Acad. Sci. 850:334–43 [Google Scholar]
73. Ressl S, Vu BK, Vivona S, Martinelli DC, Sudhof TC, Brunger AT. 73.  2015. Structures of C1q-like proteins reveal unique features among the C1q/TNF superfamily. Structure 23:688–99 [Google Scholar]
74. Richards AA, Stephens T, Charlton HK, Jones A, Macdonald GA. 74.  et al. 2006. Adiponectin multimerization is dependent on conserved lysines in the collagenous domain: evidence for regulation of multimerization by alterations in posttranslational modifications. Mol. Endocrinol. 20:1673–87 [Google Scholar]
75. Robach P, Recalcati S, Girelli D, Campostrini N, Kempf T. 75.  et al. 2013. Serum hepcidin levels and muscle iron proteins in humans injected with low- or high-dose erythropoietin. Eur. J. Haematol. 91:74–84 [Google Scholar]
76. Roettol A, Papanikolaou G, Politou M, Alberti F, Girelli D. 76.  et al. 2003. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat. Genet. 33:21–22 [Google Scholar]
77. Ross SL, Tran L, Winters A, Lee KJ, Plewa C. 77.  et al. 2012. Molecular mechanism of hepcidin-mediated ferroportin internalization requires ferroportin lysines, not tyrosines or JAK-STAT. Cell Metab. 15:905–17 [Google Scholar]
78. Seldin MM, Lei X, Tan SY, Stanson KP, Wei Z, Wong GW. 78.  2013. Skeletal muscle-derived myonectin activates the mammalian target of rapamycin (mTOR) pathway to suppress autophagy in liver. J. Biol. Chem. 288:36073–82 [Google Scholar]
79. Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. 79.  2012. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J. Biol. Chem. 287:11968–80 [Google Scholar]
80. Seldin MM, Tan SY, Wong GW. 80.  2014. Metabolic function of the CTRP family of hormones. Rev. Endocr. Metab. Disord. 15:111–23 [Google Scholar]
81. Shapiro L, Scherer PE. 81.  1998. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr. Biol. 8:335–38 [Google Scholar]
82. Sheeran C, Weekes K, Shaw J, Pasricha SR. 82.  2014. Complications of HbH disease in adulthood. Br. J. Haematol. 167136–39
83. Shemin D, Rittenberg D. 83.  1946. The lifespan of the human red blood cell. J. Biol. Chem. 166:627–36 [Google Scholar]
84. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. 84.  2008. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 8:502–11 [Google Scholar]
85. Smith CL, Arvedson TL, Cooke KS, Dickmann LJ, Forte C. 85.  et al. 2013. IL-22 regulates iron availability in vivo through the induction of hepcidin. J. Immunol. 191:1845–55 [Google Scholar]
86. Sonnweber T, Nachbaur D, Schroll A, Nairz M, Seifert M. 86.  et al. 2014. Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB. Gut 63:1951–59 [Google Scholar]
87. Talbot NP, Lakhal S, Smith TG, Privat C, Nickol AH. 87.  et al. 2012. Regulation of hepcidin expression at high altitude. Blood 119:857–60 [Google Scholar]
88. Tamary H, Shalev H, Perez-Avraham G, Zoldan M, Levi I. 88.  et al. 2008. Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood 112:5241–44 [Google Scholar]
89. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P. 89.  et al. 2007. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat. Med. 13:1096–101 [Google Scholar]
90. Tanno T, Porayette P, Sripichai O, Noh SJ, Byrnes C. 90.  et al. 2009. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 114:181–86 [Google Scholar]
91. Taylor M, Qu A, Anderson ER, Matsubara T, Martin A. 91.  et al. 2011. Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice. Gastroenterology 140:2044–55 [Google Scholar]
92. Truksa J, Lee P, Beutler E. 92.  2009. Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness. Blood 113:688–95 [Google Scholar]
93. Truksa J, Lee P, Peng H, Flanagan J, Beutler E. 93.  2007. The distal location of the iron responsive region of the hepcidin promoter. Blood 110:3436–37 [Google Scholar]
94. Tsao TS, Murrey HE, Hug C, Lee DH, Lodish HF. 94.  2002. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J. Biol. Chem. 277:29359–62 [Google Scholar]
95. Verga Falzacappa MV, Casanovas G, Hentze MW, Muckenthaler MU. 95.  2008. A bone morphogenetic protein (BMP)-responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells. J. Mol. Med. 86:531–40 [Google Scholar]
96. Vokurka M, Krijt J, Šulc K, Nečas E. 96.  2006. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol. Res. 55:667–74 [Google Scholar]
97. Wang Y, Lam KS, Chan L, Chan KW, Lam JB. 97.  et al. 2006. Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex. J. Biol. Chem. 281:16391–400 [Google Scholar]
98. Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Revett T, Gimeno R, Lodish HF. 98.  2008. Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-γ agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem. J. 416:161–77 [Google Scholar]
99. Zhang DL, Senecal T, Ghosh MC, Ollivierre-Wilson H, Tu T, Rouault TA. 99.  2011. Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts. Blood 118:2868–77 [Google Scholar]
100. Zimmermann MB, Fucharoen S, Winichagoon P, Sirankapracha P, Zeder C. 100.  et al. 2008. Iron metabolism in heterozygotes for hemoglobin E (HbE), α-thalassemia 1, or β-thalassemia and in compound heterozygotes for HbE/β-thalassemia1′2′3. Am. J. Clin. Nutr. 88:1026–31 [Google Scholar]