Role of hepcidin in physiology and pathophysiology. Emerging experimental and clinical evidence.

Abstract

Normal iron metabolism is an inherent feature of maintaining homeostasis. There is a wide range of iron disorders, which arise from iron deficiency or overload. In addition, disturbances in iron metabolism are observed in the course of numerous chronic diseases. Since iron is an essential constituent of hemoglobin, different types of anemia are clinical manifestations of both iron deficit or excess. This seemingly contradictory statement may be elucidated by the presence of hepcidin. Hepcidin is a primary regulator of iron metabolism in the human body. By promoting ferroportin degradation, hepcidin decreases the amount of iron in the circulation due to iron sequestration in the tissues and reduced intestinal absorption. Altered hepcidin concentration is a compensatory mechanism aimed at restoring iron homeostasis in various physiologic states, including pregnancy. However, hepcidin may also participate in the pathophysiologic background of hereditary hemochromatosis, anemia of chronic disease, myelodysplastic syndromes or β-thalassemia. Moreover, hepcidin is an acute-phase protein involved in innate immunity reactions. In our paper, we provide a comprehensive review of the physiologic and pathophysiologic functions of hepcidin. We present current knowledge on the structure, physiologic role and its expression control, as well as demonstrate the contribution of hepcidin in a state of illness. We also summarize the significance of hepcidin in normal and complicated pregnancy. Emphasizing the alterations in hepcidin upon treatment of specific diseases and their position in certain pathomechanisms, we support clinicians with practical aspects related to hepcidin.