Skip to content
naulon

No retraction, correction or concern found when last checked on Oct 17, 2026.

Hepcidin and Iron in Health and Disease

Elizabeta Nemeth, Tomas Ganz

Annual Review of Medicine · 2023 · Review

doi:10.1146/annurev-med-043021-032816

Abstract

Hepcidin, the iron-regulatory hormone, determines plasma iron concentrations and total body iron content. Hepcidin, secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to plasma from intestinal iron absorption and from iron stores. Hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy. Hepcidin deficiency causes iron overload in hemochromatosis and anemias with ineffective erythropoiesis. Hepcidin excess causes iron-restrictive anemias including anemia of inflammation. The development of hepcidin diagnostics and therapeutic agonists and antagonists should improve the treatment of iron disorders.

References 86

  1. 1.

    Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW 2021. Iron deficiency. Lancet 397:233–48

    Not in our library10.1016/s0140-6736(20)32594-0

  2. 2.

    Pantopoulos K 2018. Inherited disorders of iron overload. Front. Nutr 5:103

    Not in our library10.3389/fnut.2018.00103

  3. 3.

    Park CH, Valore EV, Waring AJ, Ganz T. 2001. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem 276:7806–10

    Not in our library10.1074/jbc.m008922200

  4. 4.

    Sangkhae V, Nemeth E. 2017. Regulation of the iron homeostatic hormone hepcidin. Adv. Nutr 8:126–36

    Not in our library10.3945/an.116.013961

  5. 5.

    Ganz T, Nemeth E. 2011. Hepcidin and disorders of iron metabolism. Annu. Rev. Med 62:347–60

    Not in our library10.1146/annurev-med-050109-142444

  6. 6.

    Kautz L, Jung G, Valore EV, 2014. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat. Genet 46:678–84

    Not in our library10.1038/ng.2996

  7. 7.

    Sangkhae V, Fisher AL, Chua KJ, 2020. Maternal hepcidin determines embryo iron homeostasis in mice. Blood 136:2206–16

    Not in our library10.1182/blood.2020005745

  8. 8.

    Nemeth E, Rivera S, Gabayan V, 2004. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Investig 113:1271–76

    Not in our library10.1172/jci20945

  9. 9.

    Stefanova D, Raychev A, Arezes J, 2017. Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron. Blood 130:245–57

    Not in our library10.1182/blood-2017-03-772715

  10. 10.
  11. 11.

    Malerba M, Louis S, Cuvellier S, 2020. Epidermal hepcidin is required for neutrophil response to bacterial infection. J. Clin. Investig 130:329–34

    Not in our library10.1172/jci126645

  12. 12.

    Bessman NJ, Mathieu JRR, Renassia C, 2020. Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing. Science 368:186–89

    Not in our library10.1126/science.aau6481

  13. 13.

    Donovan A, Lima CA, Pinkus JL, 2005. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 1:191–200

    Not in our library10.1016/j.cmet.2005.01.003

  14. 14.

    Taniguchi R, Kato HE, Font J, 2015. Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin. Nat. Commun 6:8545

    Not in our library10.1038/ncomms9545

  15. 15.

    Zhang DL, Ghosh MC, Ollivierre H, 2018. Ferroportin deficiency in erythroid cells causes serum iron deficiency and promotes hemolysis due to oxidative stress. Blood 132:2078–87

    Not in our library10.1182/blood-2018-04-842997

  16. 16.

    Aschemeyer S, Qiao B, Stefanova D, 2018. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood 131:899–910

    Not in our library10.1182/blood-2017-05-786590

  17. 17.

    Qiao B, Sugianto P, Fung E, 2012. Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metab. 15:918–24

    Not in our library10.1016/j.cmet.2012.03.018

  18. 18.

    Nemeth E, Tuttle MS, Powelson J, 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–93

    Not in our library10.1126/science.1104742

  19. 19.

    Billesbolle CB, Azumaya CM, Kretsch RC, 2020. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature 586:807–11

    Not in our library10.1038/s41586-020-2668-z

  20. 20.

    Preza GC, Ruchala P, Pinon R, 2011. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J. Clin. Investig 121:4880–88

    Not in our library10.1172/jci57693

  21. 21.

    Schwartz AJ, Das NK, Ramakrishnan SK, 2019. Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload. J. Clin. Investig 129:336–48

    Not in our library10.1172/jci122359

  22. 22.

    Fisher AL, Babitt JL. 2022. Coordination of iron homeostasis by bone morphogenetic proteins: current understanding and unanswered questions. Dev. Dyn 251:26–46

    Not in our library10.1002/dvdy.372

  23. 23.

    Silvestri L, Nai A, Dulja A, Pagani A. 2019. Hepcidin and the BMP-SMAD pathway: an unexpected liaison. Vitam. Horm 110:71–99

    Not in our library10.1016/bs.vh.2019.01.004

  24. 24.

    Canali S, Zumbrennen-Bullough KB, Core AB, 2017. Endothelial cells produce bone morphogenetic protein 6 required for iron homeostasis in mice. Blood 129:405–14

    Not in our library10.1182/blood-2016-06-721571

  25. 25.

    Canali S, Wang CY, Zumbrennen-Bullough KB, 2017. Bone morphogenetic protein 2 controls iron homeostasis in mice independent of Bmp6. Am. J. Hematol 92:1204–13

    Not in our library10.1002/ajh.24888

  26. 26.

    Kautz L, Meynard D, Monnier A, 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

    Not in our library10.1182/blood-2008-03-143354

  27. 27.

    Kautz L, Jung G, Du X, 2015. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of beta-thalassemia. Blood 126:2031–37

    Not in our library10.1182/blood-2015-07-658419

  28. 28.

    Wang CY, Xu Y, Traeger L, 2020. Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from binding to the BMP type I receptor ALK3. Blood 135:453–56

    Not in our library10.1182/blood.2019002620

  29. 29.

    Artuso I, Pettinato M, Nai A, 2019. Transient decrease of serum iron after acute erythropoietin treatment contributes to hepcidin inhibition by ERFE in mice. Haematologica 104:e87–90

    Not in our library10.3324/haematol.2018.199810

  30. 30.

    Gonzalez-Fernandez D, Nemeth E, Pons EDC, 2021. INTERGROWTH-21 identifies high prevalence of low symphysis-fundal height in indigenous pregnant women experiencing multiple infections, nutrient deficiencies, and inflammation: the Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) cohort. Curr. Dev. Nutr 5:nzab012

    Not in our library10.1093/cdn/nzab012

  31. 31.

    Armitage AE, Eddowes LA, Gileadi U, 2011. Hepcidin regulation by innate immune and infectious stimuli. Blood 118:4129–39

    Not in our library10.1182/blood-2011-04-351957

  32. 32.

    Kim A, Fung E, Parikh SG, 2014. A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin. Blood 123:1129–36

    Not in our library10.1182/blood-2013-08-521419

  33. 33.

    Ganz T 2019. Anemia ofinflammation. N. Engl. J. Med 381:1148–57

    Not in our library10.1056/nejmra1804281

  34. 34.

    Peters HP, Laarakkers CM, Pickkers P, 2013. Tubular reabsorption and local production of urine hepcidin-25. BMC Nephrol. 14:70

    Not in our library10.1186/1471-2369-14-70

  35. 35.

    Zaritsky J, Young B, Gales B, 2010. Reduction of serum hepcidin by hemodialysis in pediatric and adult patients. Clin. J. Am. Soc. Nephrol 5:1010–14

    Not in our library10.2215/cjn.08161109

  36. 36.

    Anderson GJ, Bardou-Jacquet E. 2021. Revisiting hemochromatosis: genetic versus phenotypic manifestations. Ann. Transl. Med 9:731

    Not in our library10.21037/atm-20-5512

  37. 37.

    Knutson MD. 2019. Non-transferrin-bound iron transporters. Free Radic. Biol. Med 133:101–11

    Not in our library10.1016/j.freeradbiomed.2018.10.413

  38. 38.

    Cooray SD, Heerasing NM, Selkrig LA, 2018. Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report. J. Med. Case Rep 12:18

    Not in our library10.1186/s13256-017-1526-6

  39. 39.

    Girelli D, Trombini P, Busti F, 2011. A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis. Haematologica 96:500–6

    Not in our library10.3324/haematol.2010.033449

  40. 40.

    Girelli D, Busti F, Brissot P, 2022. Hemochromatosis classification: update and recommendations by the BIOIRON Society. Blood 139:3018–29

    Not in our library10.1182/blood.2021011338

All 86 references

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.