Cell Biology International ISSN 1065-6995 doi: 10.1002/cbin.10505 REVIEW Hepcidin and its potential clinical utility Attila Miseta 1 , Judit Nagy 2 , Tamas Nagy 1 , Viktor Soma Po or 3 , Zsuzsanna Fekete 4 and Katalin Sipos 5 * 1 Department of Laboratory Medicine, Faculty of Medical Sciences, University of P ecs, 7624 Ifjusag Street 13. Pecs, Hungary 2 Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences, University of P ecs, 7624 Ifjusag Street 13. Pecs, Hungary 3 Department of Forensic Medicine, Faculty of Medical Sciences, University of P ecs, 7624 Szigeti Street 12. Pecs, Hungary 4 Department of Medical Biology, Faculty of Medical Sciences, University of P ecs, 7624 Szigeti Street 12. Pecs, Hungary 5 Department of Pharmaceutical Biology, Faculty of Medical Sciences, University of P ecs, 7624 Rokus Street 2. Pecs, Hungary Abstract A number of pathophysiological conditions are related to iron metabolism disturbances. Some of them are well known, others are newly discovered or special. Hepcidin is a newly identified iron metabolism regulating hormone, which could be a promising biomarker for many disorders. In this review, we provide background information about mammalian iron metabolism, cellular iron trafficking, and the regulation of expression of hepcidin. Beside these molecular biological processes, we summarize the methods that have been used to determine blood and urine hepcidin levels and present those pathological conditions (cancer, inflammation, neurological disorders) when hepcidin measurement may have clinical relevance. Keywords: diagnostics; hepcidin; iron homeostasis; liver; prohepcidin Introduction Iron is one of the essential transition metals not just for humans but practically for all living organisms. However, iron- ion in its free form is potentially toxic, may damage cellular macromolecules leading to tissue injury and disease. To minimize the risk of toxicity, living organisms developed potent biological chelators that maintain the availability of iron while transport is safe within and outside of the cell (Jomova and Valko, 2011). Iron is found in the body both in a functional form and as storage iron (Pantopoulos et al., 2012). About 68% of the total body iron is bound to hemoproteins and non-heme proteins and ca. 30% may be found in the complex form of the iron storage proteins ferritin and hemosiderin (Ganz, 2013). Only a small fraction of iron, the transferrin bound serum iron is measurable in the serum (Gkouvatsos et al., 2012). Unfortu- nately, the information value of serum iron level to assess the organism’s overall iron status is limited (Cook, 1999). Over the years, several diagnostic markers have been implemented to assess the iron status, including transferrin level, transferrin saturation, ferritin level, and soluble transferrin receptor. Albeit these laboratory parameters substantially advanced the differential diagnosis of disorders involving iron metabolism, there is still room to improve the diagnostic arsenal. Iron metabolism is a complex system still not known in every detail, and it is also influencing and influenced by many physiological and patho-physiological processes such as inflammation, malignancy, or even neurologic disorders (Camaschella, 2013). The presence or the co-existence of these conditions significantly lessens the specificity and usefulness of the presently available iron status biomarkers. Hepcidin is a recently discovered peptide hormone, which is (yet) the only known regulatory hormone of the iron homeostasis (Lesbordes-Brion et al., 2006). Hepcidin regulates iron transport by binding to the iron transporter ferroportin and upon binding, initiates the internalization and degradation of ferroportin. This process eventually leads to the decrease of available circulating iron levels (Figure 1). Revealing the regulation of hepcidin expression provides at least two benefits: (1) it improves our understanding of the regulation of iron metabolism and (2) we can use the à Corresponding author: e-mail: katalin.sipos@aok.pte.hu Abbreviations: AA, amino acid; A1AT, alpha1 antitrypsine; A2MG, alpha2 macroglobuline; BBB, blood brain barrier; BMCEs, brain microvascular endothelial cells; BMP, bone morphogenetic protein; CNS, central nervous system; DMT1, divalent metal trasporter1; ER, endoplasmic reticulum; HAMP, hepcidin antimicrobila peptide; HFE protein, human hemochromatosis protein; IL-6, interleukin-6; IRP/IRE, iron-regulatory protein/iron-responsive element; JAK/STAT, Janus kinase/signal transducers and activators of transcription; MS, mass spectrometry; sTfR, soluble transefrrine receptor; TfR, transferrin receptor 1 Cell Biol Int 9999 (2015) 1–12 © 2015 International Federation for Cell Biology