A tincture of hepcidin cures all: the potential for hepcidin therapeutics

Abstract

Iron overload as a result of blood transfusions and excessive intestinal iron absorption can be a complication of chronic anemias such as β-thalassemia. Inappropriately low levels of hepcidin, a negative regulator of iron absorption and recycling, underlie the pathophysiology of the intestinal hyperabsorption. In this issue of the JCI, Gardenghi et al. demonstrate that increasing hepcidin expression to induce iron deficiency in murine β-thalassemia not only mitigates the iron overload, but also the severity of the anemia. These data illustrate the therapeutic potential of modulating hepcidin expression in diseases associated with altered iron metabolism.

Figure 1. Potential ways in which hepcidin expression and activity could be modulated pharmacologically.

Shown in a schematized hepatocyte are several pathways leading to hepcidin expression. BMP6 stimulates hepcidin expression in a pathway dependent upon HJV, BMP receptors (BMPRs), and SMAD activation; Tmprss6 cleaves membrane-bound HJV, producing soluble HJV (sHJV). IL-6 stimulates hepcidin synthesis via STAT activation. For simplicity, not all factors involved with hepcidin expression are shown.