Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. Genetic alterations influence the serum hepcidin concentration, which can lead to an iron overload in tissues, as observed in haemochromatosis, in which serum hepcidin or defective hepcidin synthesis is observed. Another genetic imbalance of iron is iron-refractory anaemia, in which serum concentrations of hepcidin are increased, precluding the flow and efflux of extra- and intracellular iron. During the pathogenesis of certain diseases, the resulting oxidative stress, as well as the increase in inflammatory cytokines, influences the transcription of the HAMP gene to generate a secondary anaemia due to the increase in the serum concentration of hepcidin. To date, there is no available drug to inhibit or enhance hepcidin transcription, mostly due to the cytotoxicity described in the in vitro models. The proposed therapeutic targets are still in the early stages of clinical trials. Some candidates are promising, such as heparin derivatives and minihepcidins. This review describes the main pathways of systemic and genetic regulation of hepcidin, as well as its influence on the disorders related to iron metabolism.

Evstatiev R, Gasche C: Iron sensing and signalling. Gut 2012;61:933-952.
Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K: LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000;480:147-150.
Park CH, Valore EV, Waring AJ, Ganz T: Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806-7810.
Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-2093.
Kaiser L, Davis JM, Patterson J, Johnson AL, Bohart G, Olivier NB, Schwartz KA: Iron sufficient to cause hepatic fibrosis and ascites does not cause cardiac arrhythmias in the gerbil. Transl Res 2009;154:202-213.
Fleming MD: The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Hematology Am Soc Hematol Educ Program 2008, pp 151-158.
Ganz T, Nemeth E: Hepcidin and iron homeostasis. Biochim Biophys Acta 2012;1823:1434-1443.
Piperno A, Galimberti S, Mariani R, Pelucchi S, Ravasi G, Lombardi C, Bilo G, Revera M, Giuliano A, Faini A, Mainini V, Westerman M, Ganz T, Valsecchi MG, Mancia G, Parati G; HIGHCARE investigators: Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood 2011;117:2953-2959.
Ramos E, Kautz L, Rodriguez R, Hansen M, Gabayan V, Ginzburg Y, Roth MP, Nemeth E, Ganz T: Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice. Hepatology 2011;53:1333-1341.
Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S: Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108:3730-3735.
Inamura J, Ikuta K, Jimbo J, Shindo M, Sato K, Torimoto Y, Kohgo Y: Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines. Hepatol Res 2005;33:198-205.
Ganz T: Hepcidin and iron regulation, 10 years later. Blood 2011;117:4425-4433.
Pietrangelo A: Genetics, genetic testing, and management of hemochromatosis: 15 years since hepcidin. Gastroenterology 2015;149:1240-1251.
Gozzelino R, Arosio P: Iron homeostasis in health and disease. Int J Mol Sci 2016;17:130.
Drakesmith H, Prentice A: Viral infection and iron metabolism. Nat Rev Microbiol 2008;6:541-552.
Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loréal O: A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001;276:7811-7819.
Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S: Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002;99:4596-4601.
Sow FB, Florence WC, Satoskar AR, Schlesinger LS, Zwilling BS, Lafuse WP: Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis. J Leukoc Biol 2007;82:934-945.
Kulaksiz H, Fein E, Redecker P, Stremmel W, Adler G, Cetin Y: Pancreatic beta-cells express hepcidin, an iron-uptake regulatory peptide. J Endocrinol 2008;197:241-249.
Addo L, Ikuta K, Tanaka H, Toki Y, Hatayama M, Yamamoto M, Ito S, Shindo M, Sasaki Y, Shimonaka Y, Fujiya M, Kohgo Y: The three isoforms of hepcidin in human serum and their processing determined by liquid chromatography-tandem mass spectrometry (LC-tandem MS). Int J Hematol 2016;103:34-43.
Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, Iannelli A, Staccini-Myx A, Casanova D, Ben Amor I, Saint-Paul MC, Huet PM, Sadoul JL, Gugenheim J, Srai SK, Tran A, Le Marchand-Brustel Y: Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006;131:788-796.
Li Z, Hong WS, Qiu HT, Zhang YT, Yang MS, You XX, Chen SX: Cloning and expression of two hepcidin genes in the mudskipper (Boleophthalmus pectinirostris) provides insights into their roles in male reproductive immunity. Fish Shellfish Immunol 2016;56:239-247.
Chaithanya ER, Philip R, Sathyan N, Anil Kumar PR, Antony SP, Sanjeevan VN, Bright Singh IS: A novel isoform of the hepatic antimicrobial peptide, hepcidin (Hepc-CB1), from a deep-sea fish, the spinyjaw greeneye Chlorophthalmus bicornis (Norman, 1939): molecular characterisation and phylogeny. Probiotics Antimicrob Proteins 2013;5:1-7.
Anderson CP, Shen M, Eisenstein RS, Leibold EA: Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta 2012;1823:1468-1483.
Neves JV, Caldas C, Vieira I, Ramos MF, Rodrigues PN: Multiple hepcidins in a teleost fish, Dicentrarchus labrax: different hepcidins for different roles. J Immunol 2015;195:2696-2709.
Alaunyte I, Stojceska V, Plunkett A: Iron and the female athlete: a review of dietary treatment methods for improving iron status and exercise performance. J Int Soc Sports Nutr 2015;12:38.
Markova V, Norgaard A, Jørgensen KJ, Langhoff-Roos J: Treatment for women with postpartum iron deficiency anaemia. Cochrane Database Syst Rev 2015;8:CD010861.
Das JK, Salam RA, Kumar R, Bhutta ZA: Micronutrient fortification of food and its impact on woman and child health: a systematic review. Syst Rev 2013;2:67.
Muñoz M, García-Erce JA, Remacha AF: Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis. J Clin Pathol 2011;64:281-286.
Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M: Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci USA 2005;102:1324-1328.
Koskenkorva-Frank TS, Weiss G, Koppenol WH, Burckhardt S: The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radic Biol Med 2013;65:1174-1194.
Krishnamurthy P, Xie T, Schuetz JD: The role of transporters in cellular heme and porphyrin homeostasis. Pharmacol Ther 2007;114:345-358.
Chen H, Attieh ZK, Syed BA, Kuo YM, Stevens V, Fuqua BK, Andersen HS, Naylor CE, Evans RW, Gambling L, Danzeisen R, Bacouri-Haidar M, Usta J, Vulpe CD, McArdle HJ: Identification of zyklopen, a new member of the vertebratemulticopper ferroxidase family, and characterization in rodents and human cells. J Nutr 2010;140:1728-1735.
Wang J, Pantopoulos K: Regulation of cellular iron metabolism. Biochem J 2011;434:365-381.
Vashchenko G, MacGillivray RT: Multi-copper oxidases and human iron metabolism. Nutrients 2013;5:2289-2313.
Soe-Lin S, Apte SS, Andriopoulos B Jr, Andrews MC, Schranzhofer M, Kahawita T, Garcia-Santos D, Ponka P: Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc Natl Acad Sci USA 2009;106:5960-5965.
Arosio P, Levi S: Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 2010;1800:783-792.
Hentze MW, Muckenthaler MU, Galy B, Camaschella C: Two to tango: regulation of mammalian iron metabolism. Cell 2010;142:24-38.
Nemeth E, Ganz T: The role of hepcidin in iron metabolism. Acta Haematol 2009;122:78-86.
De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, Daynes RA, Kushner JP, Li D, Ward DM, Kaplan J: Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest 2010;120:2395-2405.
Haase VH: Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev 2013;27:41-53.
Rieu P: Erythropoietin: receptor of stimulating agents of erythropoiesis. Nephrol Ther 2008;2:17-22.
Sinclair AM: Erythropoiesis stimulating agents: approaches to modulate activity. Biologics 2013;7:161-174.
Kuhrt D, Wojchowski DM: Emerging EPO and EPO receptor regulators and signal transducers. Blood 2015;125:3536-3541.
Camaschella C, Pagani A, Nai A, Silvestri L: The mutual control of iron and erythropoiesis. Int J Lab Hematol 2016;38:20-26.
Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S: The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002;110:1037-1044.
Ganz T, Nemeth E: Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol 2006;290:199-203.
Shah YM, Xie L: Hypoxia-inducible factors link iron homeostasis and erythropoiesis. Gastroenterology 2014;146:630-642.
Leuenberger N, Barras L, Nicoli R, Robinson N, Baume N, Lion N, Barelli S, Tissot JD, Saugy M: Hepcidin as a new biomarker for detecting autologous blood transfusion. Am J Hematol 2016;91:467-472.
Leuenberger N, Bulla E, Salamin O, Nicoli R, Robinson N, Baume N, Saugy M: Hepcidin as a potential biomarker for blood doping. Drug Test Anal 2016, Epub ahead of print.
Nakanishi T, Hasuike Y, Nanami M, Yahiro M, Kuragano T: Novel iron-containing phosphate binders and anemia treatment in CKD: oral iron intake revisited. Nephrol Dial Transplant 2016;31:1588-1594.
Alamo IG, Kannan KB, Smith MA, Efron PA, Mohr AM: Characterization of erythropoietin and hepcidin in the regulation of persistent injury-associated anemia. J Trauma Acute Care Surg 2016;81:705-712.
Bonomini M, Del Vecchio L, Sirolli V, Locatelli F: New treatment approaches for the anemia of CKD. Am J Kidney Dis 2016;67:133-142.
Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T: Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014;46:678-684.
Kautz L, Jung G, Nemeth E, Ganz T: Erythroferrone contributes to recovery from anemia of inflammation. Blood 2014;124:2569-2574.
Honda H, Kobayashi Y, Onuma S, Shibagaki K, Yuza T, Hirao K, Yamamoto T, Tomosugi N, Shibata T: Associations among erythroferrone and biomarkers of erythropoiesis and iron metabolism, and treatment with long-term erythropoiesis-stimulating agents in patients on hemodialysis. PLoS One 2016;11:0151601.
Cucuianu A, Patiu M, Trifa AP, Tomuleasa C, Dima D: Redistribution of iron towards deposits in erythroblastopenic anemia as a consequence of decreased erythroferrone production. Med Hypotheses 2014;83:530-532.
Kautz L, Jung G, Du X, Gabayan V, Chapman J, Nasoff M, Nemeth E, Ganz T: Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia. Blood 2015;126:2031-2037.
Armitage AE, Eddowes LA, Gileadi U, Cole S, Spottiswoode N, Selvakumar TA, Ho LP, Townsend AR, Drakesmith H: Hepcidin regulation by innate immune and infectious stimuli. Blood 2011;118:4129-4139.
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T: IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004;113:1271-1276.
Schröder M: Endoplasmic reticulum stress responses. Cell Mol Life Sci 2008;65:862-894.
Oliveira SJ, Pinto JP, Picarote G, Costa VM, Carvalho F, Rangel M, de Sousa M, de Almeida SF: ER stress-inducible factor CHOP affects the expression of hepcidina by modulating C/EBPalpha activity. PLoS One 2009;4:6618.
Kautz L, Meynard D, Monnier A, Darnaud V, Bouvet R, Wang RH, Deng C, Vaulont S, Mosser J, Coppin H, Roth MP: Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 2008;112:1503-1509.
D'Alessio F, Hentze MW, Muckenthaler MU: The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. J Hepatol 2012;57:1052-1060.
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;8:502-511.
Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, Khovananth K, Mudd S, Mann N, Moresco EM, Beutler E, Beutler B: The serine protease TMPRSS6 is required to sense iron deficiency. Science 2008;320:1088-1092.
Lee DH, Zhou LJ, Zhou Z, Xie JX, Jung JU, Liu Y, Xi CX, Mei L, Xiong WC: Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis. Blood 2010;115:3136-3145.
Enns CA, Ahmed R, Zhang AS: Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavage. J Biol Chem 2012;287:35104-35117.
Perlstein TS, Pande R, Berliner N, Vanasse GJ: Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: association with anemia of inflammation. Blood 2011;117:2800-2806.
Kumar VA, Kujubu DA, Sim JJ, Rasgon SA, Yang PS: Vitamin D supplementation and recombinant human erythropoietin utilization in vitamin D-deficient hemodialysis patients. J Nephrol 2011;24:98-105.
Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, Nayak A, Wesseling-Perry K, Westerman M, Hollis BW, Salusky IB, Hewison M: Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol 2014;25:564-572.
Zughaier SM, Alvarez JA, Sloan JH, Konrad RJ, Tangpricha V: The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes. J Clin Transl Endocrinol 2014;1:19-25.
Smith EM, Alvarez JA, Kearns MD, Hao L, Sloan JH, Konrad RJ, Ziegler TR, Zughaier SM, Tangpricha V: High-dose vitamin D3 reduces circulating hepcidin concentrations: a pilot, randomized, double-blind, placebo-controlled trial in healthy adults. Clin Nutr 2016;pii: S0261-5614(16)30148-0.
Chiu PF, Ko SY, Chang CC: Vitamin C affects the expression of hepcidin and erythropoietin receptor in HepG2 cells. J Ren Nutr 2012;22:373-376.
Guo Xiaoqiang, Li Wenjie, Xin Qiliang, Ding Hui, Zhang Caiyun, Chang Yanzhong, Duan Xianglin: Vitamin C protective role for alcoholic liver disease in mice through regulating iron metabolism. Toxicol Ind Health 2011;27:341-348.
Díaz V, Peinado AB, Barba-Moreno L, Altamura S, Butragueño J, González-Gross M, Alteheld B, Stehle P, Zapico AG, Muckenthaler MU, Gassmann M: Elevated hepcidin serum level in response to inflammatory and iron signals in exercising athletes is independent of moderate supplementation with vitamin C and E. Physiol Rep 2015;3:12475.
Arruda SF, Siqueira EM, de Valência FF: Vitamin A deficiency increases hepcidin expression and oxidative stress in rat. Nutrition 2009;25:472-478.
Citelli M, Bittencourt LL, da Silva SV, Pierucci AP, Pedrosa C: Vitamin A modulates the expression of genes involved in iron bioavailability. Biol Trace Elem Res 2012;149:64-70.
da Cunha MS, Siqueira EM, Trindade LS, Arruda SF: Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis. J Nutr Biochem 2014;25:1035-1044.
Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K: Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 2002;7:1191-1204.
Babitt JL, Huang FW, Xia Y, Sidis Y, Andrews NC, Lin HY: Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest 2007;117:1933-1939.
Lin L, Valore EV, Nemeth E, Goodnough JB, Gabayan V, Ganz T: Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood 2007;110:2182-2189.
Mleczko-Sanecka K, Casanovas G, Ragab A, Breitkopf K, Müller A, Boutros M, Dooley S, Hentze MW, Muckenthaler MU: SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression. Blood 2010;115:2657-2665.
Rawlings JS, Rosler KM, Harrison DA: The JAK/STAT signaling pathway. J Cell Sci 2004;117:1281-1283.
Fleming RE: Hepcidin activation during inflammation: make it STAT. Gastroenterology 2007;132:447-449.
Pietrangelo A, Dierssen U, Valli L, Garuti C, Rump A, Corradini E, Ernst M, Klein C, Trautwein C: STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterology 2007;132:294-300.
Nemeth E, Preza GC, Jung CL, Kaplan J, Waring AJ, Ganz T: The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 2006;107:328-333.
Ross SL, Tran L, Winters A, Lee KJ, Plewa C, Foltz I, King C, Miranda LP, Allen J, Beckman H, Cooke KS, Moody G, Sasu BJ, Nemeth E, Ganz T, Molineux G, Arvedson TL: Molecular mechanism of hepcidin-mediated ferroportin internalization requires ferroportin lysines, not tyrosines or JAK-STAT. Cell Metab 2012;15:905-917.
Pantopoulos K: Function of the hemochromatosis protein HFE: lessons from animal models. World J Gastroenterol 2008;14:6893-6901.
Pietrangelo A, Caleffi A, Henrion J, Ferrara F, Corradini E, Kulaksiz H, Stremmel W, Andreone P, Garuti C: Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. Gastroenterology 2005;128:470-479.
Speletas M, Kioumi A, Loules G, Hytiroglou P, Tsitouridis J, Christakis J, Germenis AE: Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV. Blood Cells Mol Dis 2008;40:353-359.
Altès A, Bach V, Ruiz A, Esteve A, Felez J, Remacha AF, Sardà MP, Baiget M: Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene. Ann Hematol 2009;88:951-955.
European Association for the Study of the Liver: EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol 2010;53:3-22.
Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, Loukopoulos D, Camaschella C: Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 2003;33:21-22.
Hattori A, Tomosugi N, Tatsumi Y, Suzuki A, Hayashi K, Katano Y, Inagaki Y, Ishikawa T, Hayashi H, Goto H, Wakusawa S: Identification of a novel mutation in the HAMP gene that causes non-detectable hepcidin molecules in a Japanese male patient with juvenile hemochromatosis. Blood Cells Mol Dis 2012;48:179-182.
Bardou-Jacquet E, Philip J, Lorho R, Ropert M, Latournerie M, Houssel-Debry P, Guyader D, Loréal O, Boudjema K, Brissot P: Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis. Hepatology 2014;59:839-847.
Drakesmith H, Schimanski LM, Ormerod E, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR: Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 2005;106:1092-1097.
Fernandes A, Preza GC, Phung Y, De Domenico I, Kaplan J, Ganz T, Nemeth E: The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood 2009;114:437-443.
Qiao B, Sugianto P, Fung E, Del-Castillo-Rueda A, Moran-Jimenez MJ, Ganz T, Nemeth E: Hepcidin-induced endocytosis of ferroportin is dependent on ferroportina ubiquitination. Cell Metab 2012;15:918-924.
Altamura S, Kessler R, Gröne HJ, Gretz N, Hentze MW, Galy B, Muckenthaler MU: Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload. Cell Metab 2014;20:359-367.
Sham RL, Phatak PD, Nemeth E, Ganz T: Hereditary hemochromatosis due to resistance to hepcidin: high hepcidin concentrations in a family with C326S ferroportin mutation. Blood 2009;114:493-494.
Pietrangelo A: The ferroportin disease. Blood Cells Mol Dis. 2004;32:131-138.
Praschberger R, Schranz M, Griffiths WJ, Baumgartner N, Hermann M, Lomas DJ, Pietrangelo A, Cox TM, Vogel W, Zoller H: Impact of D181V and A69T on the function of ferroportin as an iron export pump and hepcidin receptor. Biochim Biophys Acta 2014;1842:1406-1412.
Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, Mayo MM, Samuel SM, Strouse JJ, Markianos K, Andrews NC, Fleming MD: Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008;40:569-571.
Folgueras AR, de Lara FM, Pendás AM, Garabaya C, Rodríguez F, Astudillo A, Bernal T, Cabanillas R, López-Otín C, Velasco G: Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood 2008;112:2539-2545.
De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, Gouya L, Camaschella C, Beaumont C: Iron refractory iron deficiency anemia. Haematologica 2013;98:845-853.
Kodama K, Noguchi A, Adachi H, Hebiguchi M, Yano M, Takahashi T: Novel mutation in the TMPRSS6 gene with iron-refractory iron deficiency anemia. Pediatr Int 2014;56:41-44.
De Falco L, Silvestri L, Kannengiesser C, Morán E, Oudin C, Rausa M, Bruno M, Aranda J, Argiles B, Yenicesu I, Falcon-Rodriguez M, Yilmaz-Keskin E, Kocak U, Beaumont C, Camaschella C, Iolascon A, Grandchamp B, Sanchez M: Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies. Hum Mutat 2014;35:1321-1329.
Xiong Y, Wu Z, Yang W, Zhao X, Peng G, Tang K, Tian Z, Xing H, Rao Q, Wang M, Wang J, Zhang F: A novel splicing mutation of TMPRSS6 in a Chinese child with iron-refractory iron deficiency anaemia. Br J Haematol 2015;171:647-649.
Altamura S, D'Alessio F, Selle B, Muckenthaler MU: A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA. Biochem J 2010;431:363-371.
Yilmaz-Keskin E, Sal E, de Falco L, Bruno M, Iolascon A, Koçak U, Yenicesu I: Is the acronym IRIDA acceptable for slow responders to iron in the presence of TMPRSS6 mutations? Turk J Pediatr 2013;55:479-484.
Heeney MM, Finberg KE: Iron-refractory iron deficiency anemia (IRIDA). Hematol Oncol Clin North Am 2014;28:637-652.
Lehmberg K, Grosse R, Muckenthaler MU, Altamura S, Nielsen P, Schmid H, Graubner U, Oyen F, Zeller W, Schneppenheim R, Janka GE: Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients. Ann Hematol 2013;92:387-394.
Galesloot TE, Geurts-Moespot AJ, den Heijer M, Sweep FC, Fleming RE, Kiemeney LA, Vermeulen SH, Swinkels DW: Associations of common variants in HFE and TMPRSS6 with iron parameters are independent of serum hepcidin in a general population: a replication study. J Med Genet 2013;50:593-598.
Fargion S, Valenti L, Fracanzani AL: Beyond hereditary hemochromatosis: new insights into the relationship between iron overload and chronic liver diseases. Dig Liver Dis 2011;43:89-95.
Cakir M, Erduran E, Turkmen ES, Aliyazicioglu Y, Reis GP, Cobanoglu U, Demir S: Hepcidin levels in children with chronic liver disease. Saudi J Gastroenterol 2015;21:300-305.
Milic S, Mikolasevic I, Orlic L, Devcic E, Starcevic-Cizmarevic N, Stimac D, Kapovic M, Ristic S: The role of iron and iron overload in chronic liver disease. Med Sci Monit 2016;22:2144-2151.
Ye P, Cheah IK, Halliwell B: A high-fat and cholesterol diet causes fatty liver in guinea pigs. The role of iron and oxidative damage. Free Radic Res 2013;47:602-613.
Ohtake T, Saito H, Hosoki Y, Inoue M, Miyoshi S, Suzuki Y, Fujimoto Y, Kohgo Y: Hepcidin is down-regulated in alcohol loading. Alcohol Clin Exp Res 2007;31:2-8.
Swinkels DW, Drenth JP: Hepcidin in the management of patients with mild non-hemochromatotic iron overload: fact or fiction? J Hepatol 2008;49:680-685.
Cylwik B, Chrostek L, Szmitkowski M: The effect of alcohol on the regulation of iron metabolism. Pol Merkur Lekarski 2008;25:273-275.
Liberopoulou A, Chachami G, Gatselis NK, Kyratzopoulou E, Saitis A, Gabeta S, Eliades P, Paraskeva E, Zachou K, Koukoulis GK, Mamalaki A, Dalekos GN, Simos G: Low serum hepcidin in patients with autoimmune liver diseases. PLoS One 2015;10: e0135486.
Harrison-Findik DD, Lu S: The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase. Biomolecules 2015;5:793-807.
Taes YE, Wuyts B, Boelaert JR, De Vriese AS, Delanghe JR: Prohepcidin accumulates in renal insufficiency. Clin Chem Lab Med 2004;42:387-389.
Tsuchiya K, Nitta K: Hepcidin is a potential regulator of iron status in chronic kidney disease. Ther Apher Dial 2013;17:1-8.
Macdougall IC, Malyszko J, Hider RC, Bansal SS: Current status of the measurement of blood hepcidin levels in chronic kidney disease. Clin J Am Soc Nephrol 2010;5:1681-1689.
Uehata T, Tomosugi N, Shoji T, Sakaguchi Y, Suzuki A, Kaneko T, Okada N, Yamamoto R, Nagasawa Y, Kato K, Isaka Y, Rakugi H, Tsubakihara Y: Serum hepcidin-25 levels and anemia in non-dialysis chronic kidney disease patients: a cross-sectional study. Nephrol Dial Transplant 2012;27:1076-1083.
Bârsan L, Stanciu A, Stancu S, Căpuşă C, Brătescu L, Mandache E, Radu E, Mircescu G: Bone marrow iron distribution, hepcidin, and ferroportin expression in renal anemia. Hematology 2015;20:543-552.
Xiong W, Wang L, Yu F: Regulation of cellular iron metabolism and its implications in lung cancer progression. Med Oncol 2014;31:28.
Torti SV, Torti FM: Iron and cancer: more ore to be mined. Nat Rev Cancer 2013;13:342-355.
Hohaus S, Giachelia M, Cuccaro A, Voso MT, Leone G: Iron in Hodgkin's lymphoma. Crit Rev Oncog 2013;18:463-469.
Tesfay L, Clausen KA, Kim JW, Hegde P, Wang X, Miller LD, Deng Z, Blanchette N, Arvedson T, Miranti CK, Babitt JL, Lin HY, Peehl DM, Torti FM, Torti SV: Hepcidin regulation in prostate and its disruption in prostate cancer. Cancer Res 2015;75:2254-2263.
Weizer-Stern O, Adamsky K, Margalit O, Ashur-Fabian O, Givol D, Amariglio N, Rechavi G: Hepcidin, a key regulator of iron metabolism, is transcriptionally activated by p53. Br J Haematol 2007;138:253-262.
Zhang S, Chen Y, Guo W, Yuan L, Zhang D, Xu Y, Nemeth E, Ganz T, Liu S: Disordered hepcidin-ferroportin signaling promotes breast cancer growth. Cell Signal 2014;26:2539-2550.
Pinnix ZK, Miller LD, Wang W, D'Agostino R Jr, Kute T, Willingham MC, Hatcher H, Tesfay L, Sui G, Di X, Torti SV, Torti FM: Ferroportin and iron regulation in breast cancer progression and prognosis. Sci Transl Med 2010;2:43-56.
Xue D, Zhou CX, Shi YB, Lu H, He XZ: Decreased expression of ferroportin in prostate cancer. Oncol Lett 2015;10:913-916.
Weiss G: Pathogenesis and treatment of anaemia of chronic disease. Blood Rev 2002;16:87-96.
Maes K, Nemeth E, Roodman GD, Huston A, Esteve F, Freytes C, Callander N, Katodritou E, Tussing-Humphreys L, Rivera S, Vanderkerken K, Lichtenstein A, Ganz T: In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2. Blood 2010;116:3635-3644.
Arndt U, Kaltwasser JP, Gottschalk R, Hoelzer D, Möller B: Correction of iron-deficient erythropoiesis in the treatment of anemia of crônicos disease with recombinant human erythropoietin. Ann Hematol 2005;84:159-166.
Nemeth E, Ganz T: Anemia of inflammation. Hematol Oncol Clin North Am 2014;28:671-681.
Basseri RJ, Nemeth E, Vassilaki ME, Basseri B, Enayati P, Shaye O, Bourikas LA, Ganz T, Papadakis KA: Hepcidin is a key mediator of anemia of inflammation in Crohn's disease. J Crohns Colitis 2013;7:286-291.
Abdel-Khalek MA, El-Barbary AM, Essa SA, Ghobashi AS: Serum hepcidin: a direct link between anemia of inflammation and coronary artery atherosclerosis in patients with rheumatoid arthritis. J Rheumatol 2011;38:2153-2159.
Noguchi-Sasaki M, Sasaki Y, Shimonaka Y, Mori K, Fujimoto-Ouchi K: Treatment with anti-IL-6 receptor antibody prevented increase in serum hepcidin levels and improved anemia in mice inoculated with IL-6-producing lung carcinoma cells. BMC Cancer 2016;16:270.
Crichton RR, Dexter DT, Ward RJ: Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm (Vienna) 2011;118:301-314.
Myhre O, Utkilen H, Duale N, Brunborg G, Hofer T: Metal dyshomeostasis and inflammation in Alzheimer's and Parkinson's diseases: possible impact of environmental exposures. Oxid Med Cell Longev 2013;2013:726954.
Urrutia P, Aguirre P, Esparza A, Tapia V, Mena NP, Arredondo M, González-Billault C, Núñez MT: Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem 2013;126:541-549.
Raha AA, Vaishnav RA, Friedland RP, Bomford A, Raha-Chowdhury R: The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer's disease. Acta Neuropathol Commun 2013;1:55.
Du F, Qian ZM, Luo Q, Yung WH, Ke Y: Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats. Mol Neurobiol 2015;52:101-114.
Fernández-Real JM, McClain D, Manco M: Mechanisms linking glucose homeostasis and iron metabolism toward the onset and progression of type 2 diabetes. Diabetes Care 2015;38:2169-2176.
Andrade-Oliveira V, Câmara NO, Moraes-Vieira PM: Adipokines as drug targets in diabetes and underlying disturbances. J Diabetes Res 2015;2015:681612.
Fu S, Li F, Zhou J, Liu Z: The relationship between body iron status, iron intake and gestational diabetes: a systematic review and meta-analysis. Medicine (Baltimore) 2016;95:e2383.
Aregbesola A, Voutilainen S, Virtanen JK, Aregbesola A, Tuomainen TP: Serum hepcidin concentrations and type 2 diabetes. World J Diabetes 2015;6:978-982.
Andrews M, Soto N, Arredondo-Olguín M: Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity. Nutrition 2015;31:51-57.
Suárez-Ortegón MF, Moreno M, Arbeláez A, Xifra G, Mosquera M, Moreno-Navarrete JM, Aguilar-de Plata C, Esteve E, Ricart W, Fernández-Real JM: Circulating hepcidin in type 2 diabetes: a multivariate analysis and double blind evaluation of metformin effects. Mol Nutr Food Res 2015;59:2460-2470.
Pechlaner R, Weiss G, Bansal S, Mayr M, Santer P, Pallhuber B, Notdurfter M, Bonora E, Willeit J, Kiechl S: Inadequate hepcidin serum concentrations predict incident type 2 diabetes mellitus. Diabetes Metab Res Rev 2016;32:187-192.
Gangaidzo IT, Moyo VM, Mvundura E, Aggrey G, Murphree NL, Khumalo H, Saungweme T, Kasvosve I, Gomo ZA, Rouault T, Boelaert JR, Gordeuk VR: Association of pulmonary tuberculosis with increased dietary iron. J Infect Dis 2001;184:936-939.
Vyoral D, Petrák J: Hepcidin: a direct link between iron metabolism and immunity. Int J Biochem Cell Biol 2005;37:1768-1773.
Singh B, Arora S, Agrawal P, Gupta SK: Hepcidin: a novel peptide hormone regulating iron metabolism. Clin Chim Acta 2011;412:823-830.
Marx JJ: Iron and infection: competition between host and microbes for a precious element. Best Pract Res Clin Haematol 2002;15:411-426.
Kossiva L, Gourgiotis DI, Tsentidis C, Anastasiou T, Marmarinos A, Vasilenko H, Sdogou T, Georgouli H: Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children: a single-center study. Pediatr Infect Dis J 2012;31:795-798.
Mendonça VR, Souza LC, Garcia GC, Magalhães BM, Gonçalves MS, Lacerda MV, Barral-Netto M: Associations between hepcidin and immune response in individuals with hyperbilirubinaemia and severe malaria due to Plasmodium vivax infection. Malar J 2015;14:407.
Leal SM Jr, Roy S, Vareechon C, Carrion Sd, Clark H, Lopez-Berges MS, Di Pietro A, Schrettl M, Beckmann N, Redl B, Haas H, Pearlman E: Targeting iron acquisition blocks infection with the fungal pathogens Aspergillus fumigatus and Fusarium oxysporum. PLoS Pathog 2013;9:1003436.
Mlisana K, Auld SC, Grobler A, van Loggerenberg F, Williamson C, Iriogbe I, Sobieszczyk ME, Abdool Karim SS; CAPRISA Acute Infection Study Team: Anaemia in acute HIV-1 subtype C infection. PLoS One 2008;3:1626.
Xu M, Kashanchi F, Foster A, Rotimi J, Turner W, Gordeuk VR, Nekhai S: Hepcidin induces HIV-1 transcription inhibited by ferroportin. Retrovirology 2010;7:104.
Malvoisin E, Makhloufi D, Livrozet JM: Serum hepcidin levels in women infected with HIV-1 under antiviral therapy. J Med Virol 2014;86:1656-1660.
Armitage AE, Stacey AR, Giannoulatou E, Marshall E, Sturges P, Chatha K, Smith NM, Huang X, Xu X, Pasricha SR, Li N, Wu H, Webster C, Prentice AM, Pellegrino P, Williams I, Norris PJ, Drakesmith H, Borrow P: Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections. Proc Natl Acad Sci USA 2014;111:12187-12192.
Cunha J, Masseli LMF, Ferreira JS, Spada C, Bydlowski SP: The effects of treatment on serum hepcidin and iron homeostasis in HIV-1-Infected Individuals. World J AIDS 2015;5:151-160.
Ganz T: Hepcidin and its role in regulating systemic iron metabolism. Hematology Am Soc Hematol Educ Program 2006;507:29-35.
Chen QX, Song SW, Chen QH, Zeng CL, Zheng X, Wang JL, Fang XM: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis induced acute lung injury. Crit Care 2014;18:470.
Johnson EE, Wessling-Resnick M: Iron metabolism and the innate immune response to infection. Microbes Infect 2012;14:207-216.
Ramos E, Ruchala P, Goodnough JB, Kautz L, Preza GC, Nemeth E, Ganz T: Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis. Blood 2012;120:3829-3836.
Casu C, Oikonomidou PR, Chen H, Nandi V, Ginzburg Y, Prasad P, Fleming RE, Shah YM, Valore EV, Nemeth E, Ganz T, MacDonald B, Rivella S: Minihepcidin peptides as disease modifiers in mice affected by β- thalassemia and polycythemia vera. Blood 2016;128:265-276.
Chua K, Fung E, Micewicz ED, Ganz T, Nemeth E, Ruchala P: Small cyclic agonists of iron regulatory hormone hepcidin. Bioorg Med Chem Lett 2015;25:4961-4969.
Fung E, Chua K, Ganz T, Nemeth E, Ruchala P: Thiol-derivatized minihepcidins retain biological activity. Bioorg Med Chem Lett 2015;25:763-766.
Silvestri L: Inhibiting the hepcidin inhibitor for treatment of iron overload. Blood 2013;121:1068-1069.
Schmidt PJ, Toudjarska I, Sendamarai AK, Racie T, Milstein S, Bettencourt BR, Hettinger J, Bumcrot D, Fleming MD: An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe-/- mice and ameliorates anemia and iron overload in murine β- thalassemia intermedia. Blood 2013;121:1200-1208.
Schmidt PJ, Racie T, Westerman M, Fitzgerald K, Butler JS, Fleming MD: Combination therapy with a Tmprss6 RNAi-therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of β-thalassemia intermedia. Am J Hematol 2015;90:310-313.
Corradini E, Schmidt PJ, Meynard D, Garuti C, Montosi G, Chen S, Vukicevic S, Pietrangelo A, Lin HY, Babitt JL: BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice. Gastroenterology 2010;139:1721-1729.
Hashizume M, Uchiyama Y, Horai N, Tomosugi N, Mihara M: Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production. Rheumatol Int 2010;30:917-923.
Isaacs JD, Harari O, Kobold U, Lee JS, Bernasconi C: Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis. Arthritis Res Ther 2013;15:R204.
Song SN, Iwahashi M, Tomosugi N, Uno K, Yamana J, Yamana S, Isobe T, Ito H, Kawabata H, Yoshizaki K: Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients. Arthritis Res Ther 2013;15:141.
Casper C, Chaturvedi S, Munshi N, Wong R, Qi M, Schaffer M, Bandekar R, HallB, Van de Velde H, Vermeulen J, Reddy M, Van Rhee F: Analysis of inflammatory and anemia-related biomarkers in a randomized, double-blind, placebo-controlled study of siltuximab (anti-il6 monoclonal antibody) in patients with multicentric Castleman disease. Clin Cancer Res 2015;21:4294-4304.
Fatih N, Camberlein E, Island ML, Corlu A, Abgueguen E, Détivaud L, Leroyer P, Brissot P, Loréal O: Natural and synthetic STAT3 inhibitors reduce hepcidina expression in differentiated mouse hepatocytes expressing the active phosphorylated STAT3 form. J Mol Med (Berl) 2010;88:477-486.
Zhang SP, Wang Z, Wang LX, Liu SJ: AG490: an inhibitor of hepcidin expression in vivo. World J Gastroenterol 2011;17:5032-5034.
Schwoebel F, van Eijk LT, Zboralski D, Sell S, Buchner K, Maasch C, Purschke WG, Humphrey M, Zöllner S, Eulberg D, Morich F, Pickkers P, Klussmann S: The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood 2013;121:2311-2315.
Van Eijk LT, John AS, Schwoebel F, Summo L, Vauléon S, Zöllner S, Laarakkers CM, Kox M, van der Hoeven JG, Swinkels DW, Riecke K, Pickkers P: Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood 2014;124:2643-2646.
Vater A, Klussmann S: Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics. Drug Discov Today 2015;20:147-155.
Mayeur C, Kolodziej SA, Wang A, Xu X, Lee A, Yu PB, Shen J, Bloch KD, Bloch DB: Oral administration of a bone morphogenetic protein type I receptor inhibitor prevents the development of anemia of inflammation. Haematologica 2015;100:68-71.
Sun CC, Vaja V, Chen S, Theurl I, Stepanek A, Brown DE, Cappellini MD, Weiss G, Hong CC, Lin HY, Babitt JL: A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats. Nephrol Dial Transplant 2013;28:1733-1743.
Theurl M, Nairz M, Schroll A, Sonnweber T, Asshoff M, Haschka D, Seifert M, Willenbacher W, Wilflingseder D, Posch W, Murphy AT, Witcher DR, Theurl I, Weiss G: Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats. Haematologica 2014;99:1516-1524.
Steinbicker AU, Bartnikas TB, Lohmeyer LK, Leyton P, Mayeur C, Kao SM, Pappas AE, Peterson RT, Bloch DB, Yu PB, Fleming MD, Bloch KD: Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood 2011;118:4224-4230.
Böser P, Seemann D, Liguori MJ, Fan L, Huang L, Hafner M, Popp A, Mueller BK: Anti-repulsive guidance molecule C (RGMc) antibodies increases serum iron in rats and cynomolgus monkeys by hepcidin downregulation. AAPS J 2015;17:930-938.
Blanchette NL, Manz DH, Torti FM, Torti SV: Modulation of hepcidin to treat iron deregulation: potential clinical applications. Expert Rev Hematol 2016;9:169-186.
Theurl I, Schroll A, Sonnweber T, Nairz M, Theurl M, Willenbacher W, Eller K, Wolf D, Seifert M, Sun CC, Babitt JL, Hong CC, Menhall T, Gearing P, Lin HY, Weiss G: Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood 2011;118:4977-4984.
Fung E, Nemeth E: Manipulation of the hepcidin pathway for therapeutic purposes. Haematologica 2013;98:1667-1676.
Sasu BJ, Cooke KS, Arvedson TL, Plewa C, Ellison AR, Sheng J, Winters A, Juan T, Li H, Begley CG, Molineux G: Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood 2010;115:3616-3624.
Xiao JJ, Krzyzanski W, Wang YM, Li H, Rose MJ, Ma M, Wu Y, Hinkle B, Perez-Ruixo JJ: Pharmacokinetics of anti-hepcidin monoclonal antibody Ab 12B9m and hepcidin in cynomolgus monkeys. AAPS J 2010;12:646-657.
Cooke KS, Hinkle B, Salimi-Moosavi H, Foltz I, King C, Rathanaswami P, Winters A, Steavenson S, Begley CG, Molineux G, Sasu BJ: A fully human anti-hepcidin antibody modulates iron metabolism in both mice and nonhuman primates. Blood 2013;122:3054-3061.
Poli M, Girelli D, Campostrini N, Maccarinelli F, Finazzi D, Luscieti S, Nai A, Arosio P: Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo. Blood 2011;117:997-1004.
Poli M, Asperti M, Ruzzenenti P, Mandelli L, Campostrini N, Martini G, Di Somma M, Maccarinelli F, Girelli D, Naggi A, Arosio P: Oversulfated heparins with low anticoagulant activity are strong and fast inhibitors of hepcidin expression in vitro and in vivo. Biochem Pharmacol 2014;92:467-475.
Asperti M, Naggi A, Esposito E, Ruzzenenti P, Di Somma M, Gryzik M, Arosio P, Poli M: High sulfation and a high molecular weight are important for anti-hepcidin activity of heparin. Front Pharmacol 2016;6:316.
Schlehuber S, Skerra A: Lipocalins in drug discovery: from natural ligand-binding proteins to “anticalins”. Drug Discov Today 2005;10:23-33.
Poli M, Asperti M, Ruzzenenti P, Regoni M, Arosio P: Hepcidin antagonists for potential treatments of disorders with hepcidin excess. Front Pharmacol 2014;5:86.
Jiang F, Yu WJ, Wang XH, Tang YT, Guo L, Jiao XY: Regulation of hepcidina through GDF-15 in cancer-related anemia. Clin Chim Acta 2014;428:14-19.
Fujiwara T, Ikeda T, Nagasaka Y, Okitsu Y, Katsuoka Y, Fukuhara N, Onishi Y, Ishizawa K, Ichinohasama R, Tomosugi N, Harigae H: A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One 2013;8:75568.
Wittrup A, Lieberman J: Knocking down disease: a progress report on siRNA therapeutics. Nat Rev Genet 2015;16:543-552.
De Domenico I, Lo E, Ward DM, Kaplan J: Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2. Proc Natl Acad Sci USA 2009;106:3800-3805.
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