Iron Metabolism and Hepcidin

Abstract

Iron is essential for a variety of cellular functions, but it can cause tissue damage when present in excess. Due to its dual nature, the amount of iron in the body should be strictly controlled. One of the key molecules for maintaining iron homeostasis in the body is hepcidin, a peptide hormone mainly produced in the liver. Expression of hepcidin is upregulated by iron loading and inflammatory cytokines such as interleukin-6, and down-regulated by hypoxia and erythropoietic stimuli. Hepcidin decreases both iron absorption from the intestine and iron release from macrophages through down-regulation of ferroportin, the only iron exporter of the cells. HFE , TFR2 (transferrin receptor 2) and HJV (hemojuvelin) are expressed in the liver, and these are related to the iron sensing machinery. Mutations of one of these genes or HAMP (hepcidin) gene cause down-regulation of hepcidin expression, resulting in increased iron absorption from the intestine and iron accumulation in the body (hereditary hemochromatosis). In contrast, mutations of TMPRSS6 (matriptase-2) gene cause an increase of hepcidin expression, resulting in hereditary iron deficiency anemia. Hepcidin is also upregulated in chronic inflammation, causing anemia of chronic disease. In this review, I will attempt to provide an integrated view of physiology and pathophysiology of iron metabolism in the body by focusing on hepcidin.