Hepcidin - A novel biomarker with changing trends

Arunava Kali, Marie Victor Pravin Charles, Rathan Shetty Kolkebail Seetharam, Arunava Kali, Marie Victor Pravin Charles, Rathan Shetty Kolkebail Seetharam

Abstract

Hepcidin is a novel peptide hormone of hepatic origin. It has a crucial role in iron metabolism. The causative association of this peptide in anemia and iron overloading states has been well established. Current research has expanded the diagnostic implications of hepcidin in other medical conditions. Increased serum hepcidin has been reported in neoplastic diseases, inflammation, and sepsis. However, the clinical use of hepcidin as a biomarker is limited owing to nonavailability of an appropriate diagnostic test. Assays for serum and urine hepcidin estimation have been developed recently, which are likely to facilitate the use of hepcidin in research as well as in patient care in the near future.

Keywords: Biomarker; hepcidin; iron metabolism; malignancy; sepsis.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Regulation of iron absorption, distribution, and recycling by hepcidin. Enterocyte (a), macrophage (b), and liver (c) contribute to the plasma iron pool by iron efflux, which is utilized for erythropoiesis (black arrows). Plasma iron loading, decreased erythropoiesis in bone marrow and inflammatory cytokines (IL-6) induce hepatic hepcidin production (blue arrows). Hepcidin inhibits intestinal iron absorption and iron mobilization from hepatic and reticuloendothelial iron stores (red arrows)

References

    1. Nicolae CD, Coman OA, Ene C, Nicolae I, Fulga I. Hepcidin in neoplastic disease. J Med Life. 2013;6:355–60.
    1. Robson KJ. Hepcidin and its role in iron absorption. Gut. 2004;53:617–9.
    1. Fleming RE, Sly WS. Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad Sci U S A. 2001;98:8160–2.
    1. Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol. 2006;290:G199–203.
    1. Ashrafian H. Hepcidin: The missing link between hemochromatosis and infections. Infect Immun. 2003;71:6693–700.
    1. Lasocki S, Longrois D, Montravers P, Beaumont C. Hepcidin and anemia of the critically ill patient: Bench to bedside. Anesthesiology. 2011;114:688–94.
    1. Cizmeci MN, Kara S, Kanburoglu MK, Simavli S, Duvan CI, Tatli MM. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis. Med Hypotheses. 2014;82:310–2.
    1. Dudkowiak R, Neubauer K, Poniewierka E. Hepcidin and its role in inflammatory bowel disease. Adv Clin Exp Med. 2013;22:585–91.
    1. Kemna EH, Tjalsma H, Willems HL, Swinkels DW. Hepcidin: From discovery to differential diagnosis. Haematologica. 2008;93:90–7.
    1. Piperno A, Mariani R, Trombini P, Girelli D. Hepcidin modulation in human diseases: From research to clinic. World J Gastroenterol. 2009;15:538–51.
    1. Camaschella C, Silvestri L. Molecular mechanisms regulating hepcidin revealed by hepcidin disorders. Scientific World Journal. 2011;11:1357–66.
    1. Young B, Zaritsky J. Hepcidin for clinicians. Clin J Am Soc Nephrol. 2009;4:1384–7.
    1. Palaneeswari MS, Ganesh M, Karthikeyan T, Devi AJ, Mythili SV. Hepcidin-minireview. J Clin Diagn Res. 2013;7:1767–71.
    1. Laarakkers CM, Wiegerinck ET, Klaver S, Kolodziejczyk M, Gille H, Hohlbaum AM, et al. Improved mass spectrometry assay for plasma hepcidin: Detection and characterization of a novel hepcidin isoform. PLoS One. 2013;8:e75518.
    1. Ford BA, Eby CS, Scott MG, Coyne DW. Intra-individual variability in serum hepcidin precludes its use as a marker of iron status in hemodialysis patients. Kidney Int. 2010;78:769–73.
    1. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: Implications for the anemia of chronic disease. Blood. 2002;100:3776–81.
    1. Orlandi R, De Bortoli M, Ciniselli CM, Vaghi E, Caccia D, Garrisi V, et al. Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer. Ann Oncol. 2013;25:352–7.
    1. Tanno T, Rabel A, Alleyne M, Lee YT, Dahut WL, Gulley JL, et al. Hepcidin, anaemia, and prostate cancer. BJU Int. 2011;107:678–9.
    1. Wu XN, Su D, Wang L, Yu FL. Roles of the hepcidin-ferroportin axis and iron in cancer. Eur J Cancer Prev. 2014;23:122–33.
    1. Abd Elmonem E, Tharwa el-S, Farag MA, Fawzy A, El Shinnawy SF, Suliman S. Hepcidin mRNA level as a parameter of disease progression in chronic hepatitis C and hepatocellular carcinoma. J Egypt Natl Canc Inst. 2009;21:333–42.
    1. Maes K, Nemeth E, Roodman GD, Huston A, Esteve F, Freytes C, et al. In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2. Blood. 2010;116:3635–44.
    1. Christiansen H, Saile B, Hermann RM, Rave-Frank M, Hille A, Schmidberger H, et al. Increase of hepcidin plasma and urine levels is associated with acute proctitis and changes in hemoglobin levels in primary radiotherapy for prostate cancer. J Cancer Res Clin Oncol. 2007;133:297–304.
    1. Steegmann, Olmedillas JL. The role of iron in tumour cell proliferation. Clin Transl Oncol. 2011;13:71–6.
    1. Wang SJ, Gao C, Chen BA. Advancement of the study on iron metabolism and regulation in tumor cells. Chin J Cancer. 2010;29:451–5.
    1. Pogribny IP. Ferroportin and hepcidin: A new hope in diagnosis, prognosis, and therapy for breast cancer. Breast Cancer Res. 2010;12:314.
    1. Durigova A, Lamy PJ, Thezenas S, Pouderoux S, Montels F, Romieu G, et al. Anemia and iron biomarkers in patients with early breast cancer. Diagnostic value of hepcidin and soluble transferrin receptor quantification. Clin Chem Lab Med. 2013;51:1833–41.
    1. Kossiva L, Soldatou A, Gourgiotis DI, Stamati L, Tsentidis C. Serum hepcidin: Indication of its role as an “acute phase” marker in febrile children. Ital J Pediatr. 2013;39:25.
    1. Arabul M, Celik M, Aslan O, Torun S, Beyazit Y, Alper E, et al. Hepcidin as a predictor of disease severity in acute pancreatitis: A single center prospective study. Hepatogastroenterology. 2013;60:595–600.
    1. Basseri RJ, Nemeth E, Vassilaki ME, Basseri B, Enayati P, Shaye O, et al. Hepcidin is a key mediator of anemia of inflammation in Crohn's disease. J Crohns Colitis. 2013;7:e286–91.
    1. Wu TW, Tabangin M, Kusano R, Ma Y, Ridsdale R, Akinbi H. The utility of serum hepcidin as a biomarker for late-onset neonatal sepsis. J Pediatr. 2013;162:67–71.
    1. McClung JP, Martini S, Murphy NE, Montain SJ, Margolis LM, Thrane I, et al. Effects of a 7-day military training exercise on inflammatory biomarkers, serum hepcidin, and iron status. Nutr J. 2013;12:141.
    1. Ziemann E, Kasprowicz K, Kasperska A, Zembroń-Lacny A, Antosiewicz J, Laskowski R. Do high blood hepcidin concentrations contribute to low ferritin levels in young tennis players at the end of tournament season? J Sports Sci Med. 2013;12:249–58.
    1. Kasprowicz K, Ziemann E, Ratkowski W, Laskowski R, Kaczor JJ, Dadci R, et al. Running a 100-km ultra-marathon induces an inflammatory response but does not raise the level of the plasma iron-regulatory protein hepcidin. J Sports Med Phys Fitness. 2013;53:533–7.
    1. Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology. 2006;131:788–96.
    1. Sam AH, Busbridge M, Amin A, Webber L, White D, Franks S, et al. Hepcidin levels in diabetes mellitus and polycystic ovary syndrome. Diabet Med. 2013;30:1495–9.
    1. Kanbay A, Hasanoglu HC. A new prognostic marker for obstructive sleep apnea: Hepcidin. Med Hypotheses. 2007;69:1381–2.
    1. Walker AP, Partridge J, Srai SK, Dooley JS. Hepcidin: What every gastroenterologist should know. Gut. 2004;53:624–7.
    1. Ganz T, Nemeth E. The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders. Hematology Am Soc Hematol Educ Program 2011. 2011:538–42.
    1. Corradini E, Schmidt PJ, Meynard D, Garuti C, Montosi G, Chen S, et al. BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice. Gastroenterology. 2010;139:1721–9.
    1. Finberg KE, Whittlesey RL, Andrews NC. Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice. Blood. 2011;117:4590–9.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe