hepcidins

Summary

Summary: Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.

Top Publications

  1. Reichert C, da Cunha J, Levy D, Maselli L, Bydlowski S, Spada C. Hepcidin: Homeostasis and Diseases Related to Iron Metabolism. Acta Haematol. 2017;137:220-236 pubmed publisher
    ..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. ..
  2. Ambroszkiewicz J, Klemarczyk W, Mazur J, Gajewska J, Rowicka G, Strucińska M, et al. Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet. Biol Trace Elem Res. 2017;180:182-190 pubmed publisher
  3. Shao Y, Wang H, Liu C, Cao Q, Fu R, Wang H, et al. Transforming growth factor 15 increased in severe aplastic anemia patients. Hematology. 2017;22:548-553 pubmed publisher
    ..739, p?=?0.000). Our data indicated that GDF-15 plays an important role in iron metabolism in SAA. GDF-15 might be a novel target for SAA therapy. ..
  4. Kanamori Y, Murakami M, Sugiyama M, Hashimoto O, Matsui T, Funaba M. Interleukin-1? (IL-1?) transcriptionally activates hepcidin by inducing CCAAT enhancer-binding protein ? (C/EBP?) expression in hepatocytes. J Biol Chem. 2017;292:10275-10287 pubmed publisher
    ..In cooperation with the other pathways activated by inflammation, IL-1? pathway stimulation leads to excess production of hepcidin, which could be causative to anemia of inflammation. ..
  5. Taubert R, Hardtke Wolenski M, Noyan F, Lalanne C, Jonigk D, Schlue J, et al. Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis. PLoS ONE. 2017;12:e0179074 pubmed publisher
  6. You L, Yan C, Zheng B, Ci Y, Chang S, Yu P, et al. Astrocyte hepcidin is a key factor in LPS-induced neuronal apoptosis. Cell Death Dis. 2017;8:e2676 pubmed publisher
    ..Such a pathway is relevant to NDs in that it links inflammation, microglia and astrocytes to neuronal damage. ..
  7. Stoffel N, Zeder C, Fort E, Swinkels D, Zimmermann M, Moretti D. Prediction of human iron bioavailability using rapid c-ELISAs for human plasma hepcidin. Clin Chem Lab Med. 2017;55:1186-1192 pubmed publisher
    ..Between methods, prediction of iron bioavailability in generally healthy iron depleted subjects appears comparable. ..
  8. Isaacs J, Harari O, Kobold U, Lee J, Bernasconi C. Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis. Arthritis Res Ther. 2013;15:R204 pubmed
    ..These clinical data provide evidence of a role for IL-6 signalling in the inflammatory anaemia of RA. ..
  9. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93:1721-41 pubmed publisher
    ..This review summarizes and discusses recent progress in molecular characterization of systemic iron homeostasis and its disorders, and identifies areas for further investigation. ..

More Information

Publications53

  1. Dong Y, Jiang W, Liu Y, Wu P, Jiang J, Kuang S, et al. Threonine deficiency decreased intestinal immunity and aggravated inflammation associated with NF-?B and target of rapamycin signalling pathways in juvenile grass carp (Ctenopharyngodon idella) after infection with Aeromonas hydrophila. Br J Nutr. 2017;118:92-108 pubmed publisher
    ..05 g threonine/kg diet (4·64 g threonine/100 g protein) and 15·17 g threonine/kg diet (4·68 g threonine/100 g protein), respectively. ..
  2. Jakszyn P, Fonseca Nunes A, Lujan Barroso L, Aranda N, Tous M, Arija V, et al. Hepcidin levels and gastric cancer risk in the EPIC-EurGast study. Int J Cancer. 2017;141:945-951 pubmed publisher
    ..Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis. ..
  3. Duck K, Simpson I, Connor J. Regulatory mechanisms for iron transport across the blood-brain barrier. Biochem Biophys Res Commun. 2017;494:70-75 pubmed publisher
    ..Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field. ..
  4. Sullivan J. Do hemochromatosis mutations protect against iron-mediated atherogenesis?. Circ Cardiovasc Genet. 2009;2:652-7 pubmed publisher
  5. Jorgensen J, Yang Z, Lonnerdal B, Chantry C, Dewey K. Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or ?1-Acid Glycoprotein. J Nutr. 2017;147:1194-1199 pubmed publisher
    ..b>Conclusion: Lower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states. ..
  6. Fang Y, Shen C, Luan N, Yao H, Long C, Lai R, et al. In vivo antimalarial activity of synthetic hepcidin against Plasmodium berghei in mice. Chin J Nat Med. 2017;15:161-167 pubmed publisher
  7. Østgård R, Glerup H, Jurik A, Kragstrup T, Stengaard Pedersen K, Hetland M, et al. Hepcidin plasma levels are not associated with changes in haemoglobin in early rheumatoid arthritis patients. Scand J Rheumatol. 2017;46:441-445 pubmed publisher
    ..The changes in hepcidin were not associated with changes in haemoglobin levels. Thus, hepcidin could not be used as a prognostic marker in patients with early RA. ..
  8. Pechlaner R, Kiechl S, Mayr M, Santer P, Weger S, Haschka D, et al. Correlates of serum hepcidin levels and its association with cardiovascular disease in an elderly general population. Clin Chem Lab Med. 2016;54:151-61 pubmed publisher
  9. Addo L, Ikuta K, Tanaka H, Toki Y, Hatayama M, Yamamoto M, et al. 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 pubmed
    ..This method has enabled us to reveal fundamental characteristics of the three hepcidin isoforms in serum and may be a powerful tool for quantifying hepcidin isoform expression and processing. ..
  10. Lasocki S, Gaillard T, Rineau E. Iron is essential for living!. Crit Care. 2014;18:678 pubmed publisher
    ..This opens areas of research for sepsis treatment but also for iron deficiency or anaemia treatment, since the local and systemic iron regulation appear to be independent. ..
  11. Chen Q, Song S, Chen Q, Zeng C, Zheng X, Wang J, et al. Silencing airway epithelial cell-derived hepcidin exacerbates sepsis induced acute lung injury. Crit Care. 2014;18:470 pubmed publisher
    ..The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages. ..
  12. Ostermann M, Philips B, Forni L. Clinical review: Biomarkers of acute kidney injury: where are we now?. Crit Care. 2012;16:233 pubmed publisher
    ..We outline the major studies described to date as well as discuss potential reasons for the discrepancies observed and suggest that evolution of the field may result in success with ultimately an improvement in patient outcomes. ..
  13. Cavallaro F, Duca L, Pisani L, Rigolini R, Spina L, Tontini G, et al. Anti-TNF-Mediated Modulation of Prohepcidin Improves Iron Availability in Inflammatory Bowel Disease, in an IL-6-Mediated Fashion. Can J Gastroenterol Hepatol. 2017;2017:6843976 pubmed publisher
    ..This effect appears to be related to the modulation of the cytokine network and specifically IL-6 leading to a relevant decrease of hepcidin, a master regulator of ACD. ..
  14. Huang Y, Kuo H. Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker. Int J Mol Sci. 2017;18: pubmed publisher
    ..This review focuses on hepcidin-induced iron deficiency's relation to transient hyposideremia, anemia, and disease outcomes in KD patients, and goes on to suggest possible routes of further study. ..
  15. Ganz T, Jung G, Naeim A, Ginzburg Y, Pakbaz Z, Walter P, et al. Immunoassay for human serum erythroferrone. Blood. 2017;130:1243-1246 pubmed publisher
    ..The assay should be useful for human studies of normal and disordered erythropoiesis and its effect on iron homeostasis...
  16. Thomas D, Hinchliffe R, Briggs C, Macdougall I, Littlewood T, Cavill I. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161:639-48 pubmed publisher
  17. Colucci S, Pagani A, Pettinato M, Artuso I, Nai A, Camaschella C, et al. The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes. Blood. 2017;130:2111-2120 pubmed publisher
    ..Our results identify a novel hepcidin regulator and a potential therapeutic target to increase defective BMP signaling in disorders of low hepcidin. ..
  18. Ma W, Lu J, Jiang S, Cai D, Pan S, Jia Y, et al. Maternal protein restriction depresses the duodenal expression of iron transporters and serum iron level in male weaning piglets. Br J Nutr. 2017;117:923-929 pubmed publisher
  19. Liang L, Liu H, Yue J, Liu L, Han M, Luo L, et al. Association of Single-Nucleotide Polymorphism in the Hepcidin Promoter Gene with Susceptibility to Extrapulmonary Tuberculosis. Genet Test Mol Biomarkers. 2017;21:351-356 pubmed publisher
    ..tuberculosis lipoarabinomannan compared with cells from individuals with either the AA or AG genotypes. The G allele of the HAMP-P -582?A>G gene may play a critical role in TB susceptibility. ..
  20. Lasocki S, Longrois D, Montravers P, Beaumont C. Hepcidin and anemia of the critically ill patient: bench to bedside. Anesthesiology. 2011;114:688-94 pubmed publisher
  21. Armitage A, Pinches R, Eddowes L, Newbold C, Drakesmith H. Plasmodium falciparum infected erythrocytes induce hepcidin (HAMP) mRNA synthesis by peripheral blood mononuclear cells. Br J Haematol. 2009;147:769-71 pubmed publisher
  22. Wang C, Core A, Canali S, Zumbrennen Bullough K, Ozer S, Umans L, et al. Smad1/5 is required for erythropoietin-mediated suppression of hepcidin in mice. Blood. 2017;130:73-83 pubmed publisher
    ..Thus, Smad1 and Smad5 have overlapping functions to govern hepcidin transcription. Moreover, erythropoietin and erythroferrone target Smad1/5 signaling and require Smad1/5 to suppress hepcidin expression. ..
  23. Fukuda T, Goto R, Kiho T, Ueda K, Muramatsu S, Hashimoto M, et al. Discovery of DS79182026: A potent orally active hepcidin production inhibitor. Bioorg Med Chem Lett. 2017;27:3716-3722 pubmed publisher
    ..The optimization study of multi kinase inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model. ..
  24. Canali S, Wang C, Zumbrennen Bullough K, Bayer A, Babitt J. Bone morphogenetic protein 2 controls iron homeostasis in mice independent of Bmp6. Am J Hematol. 2017;92:1204-1213 pubmed publisher
    ..Together, these data demonstrate that in addition to BMP6, endothelial cell BMP2 has a non-redundant role in hepcidin regulation by iron. ..
  25. Kroot J, Laarakkers C, Kemna E, Biemond B, Swinkels D. Regulation of serum hepcidin levels in sickle cell disease. Haematologica. 2009;94:885-7 pubmed publisher
  26. Xie G, Zhu L, Zhang Y, Zhang Q, Yu Q. Change in iron metabolism in rats after renal ischemia/reperfusion injury. PLoS ONE. 2017;12:e0175945 pubmed publisher
    ..These findings might suggest a self-protection mechanism regulating iron homeostasis in IRI and provide a new perspective on iron metabolism in attenuating renal IRI. ..
  27. Sellam J, Kotti S, Fellahi S, Bastard J, Meyer M, Lioté F, et al. Serum hepcidin level is not an independent surrogate biomarker of disease activity or of radiographic progression in rheumatoid arthritis: results from the ESPOIR cohort. Ann Rheum Dis. 2013;72:312-4 pubmed publisher
  28. Winter W, Bazydlo L, Harris N. The molecular biology of human iron metabolism. Lab Med. 2014;45:92-102 pubmed
    ..Each ferritin molecule can contain as many as approximately 4500 ferric ions. Because the major role of iron is in hemoglobin synthesis, this review will focus on iron, iron transport, and hematopoiesis. ..
  29. Song S, Iwahashi M, Tomosugi N, Uno K, Yamana J, Yamana S, et al. Comparative evaluation of the effects of treatment with tocilizumab and TNF-? inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients. Arthritis Res Ther. 2013;15:R141 pubmed publisher
    ..In our cohort, tocilizumab was more effective than TNF-? inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production. ..
  30. Mupfudze T, Stoltzfus R, Rukobo S, Moulton L, Humphrey J, Prendergast A. Hepcidin decreases over the first year of life in healthy African infants. Br J Haematol. 2014;164:150-3 pubmed publisher
  31. Frýdlová J, Rychtarčíková Z, Gurieva I, Vokurka M, Truksa J, Krijt J. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice. PLoS ONE. 2017;12:e0186844 pubmed publisher
  32. Auguet T, Aragonès G, Berlanga A, Martínez S, Sabench F, Binetti J, et al. Hepcidin in morbidly obese women with non-alcoholic fatty liver disease. PLoS ONE. 2017;12:e0187065 pubmed publisher
  33. Heming N, Montravers P, Lasocki S. Iron deficiency in critically ill patients: highlighting the role of hepcidin. Crit Care. 2011;15:210 pubmed publisher
  34. Coffey R, Ganz T. Iron homeostasis: An anthropocentric perspective. J Biol Chem. 2017;292:12727-12734 pubmed publisher
    ..Hepcidin is feedback-regulated by iron status and strongly modulated by inflammation and erythropoietic demand. This review highlights recent advances that have changed our understanding of iron metabolism and its regulation. ..
  35. Xu Q, Langley M, Kanthasamy A, Reddy M. Epigallocatechin Gallate Has a Neurorescue Effect in a Mouse Model of Parkinson Disease. J Nutr. 2017;147:1926-1931 pubmed publisher
  36. Wallace D, McDonald C, Ostini L, Iser D, Tuckfield A, Subramaniam V. The dynamics of hepcidin-ferroportin internalization and consequences of a novel ferroportin disease mutation. Am J Hematol. 2017;92:1052-1061 pubmed publisher
    ..Our novel ferroportin antibody and assay will be valuable tools for investigating the regulation of hepcidin/ferroportin function and the development of novel approaches for the therapeutic modulation of iron homeostasis. ..
  37. Wang C, Fang Z, Zhu Z, Liu J, Chen H. Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic application in erythroid disorders. Exp Hematol. 2017;52:24-31 pubmed publisher
    ..These therapeutic strategies include suppressing or activating HAMP gene expression, mimicking or activating hepcidin activity, and blocking the ability of hepcidin to bind to its target ferroportin. ..
  38. Goto K, Sumi D, Kojima C, Ishibashi A. Post-exercise serum hepcidin levels were unaffected by hypoxic exposure during prolonged exercise sessions. PLoS ONE. 2017;12:e0183629 pubmed publisher
    ..In conclusion, endurance exercise at lower running velocity in hypoxic conditions resulted in similar post-exercise hepcidin elevations as higher running velocity in normoxic conditions. ..
  39. Steensma D, Sasu B, Sloan J, Tomita D, Loprinzi C. Serum hepcidin levels predict response to intravenous iron and darbepoetin in chemotherapy-associated anemia. Blood. 2015;125:3669-71 pubmed publisher
  40. Moreira A, Neves J, Silva T, Oliveira P, Gomes M, Rodrigues P. Hepcidin-(In)dependent Mechanisms of Iron Metabolism Regulation during Infection by Listeria and Salmonella. Infect Immun. 2017;85: pubmed publisher
    ..In this work, we compare several aspects of iron metabolism alterations induced by two different pathogens and suggest that hepcidin-(in)dependent mechanisms contribute to iron redistribution upon infection. ..
  41. Bah A, Pasricha S, Jallow M, Sise E, Wegmüller R, Armitage A, et al. Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia. J Nutr. 2017;147:1131-1137 pubmed publisher
    ..Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial was registered at www.isrctn.com as ISRCTN49285450. ..
  42. Stefanova D, Raychev A, Arezes J, Ruchala P, Gabayan V, Skurnik M, et al. Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron. Blood. 2017;130:245-257 pubmed publisher
  43. Knutson M. Iron transport proteins: Gateways of cellular and systemic iron homeostasis. J Biol Chem. 2017;292:12735-12743 pubmed publisher
    ..This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease. ..
  44. Kajarabille N, Brown C, Cucliciu A, Thapaliya G, Latunde Dada G. Bioavailability of iron multi-amino acid chelate preparation in mice and human duodenal HuTu 80 cells. Br J Nutr. 2017;117:767-774 pubmed publisher
    ..Fe absorption in mice and cells was similar for both IMAAC and FeSO4 and both compounds induce and regulate Fe metabolism genes similarly in the maintenance of homeostasis in mice. ..