The binding peptide to hepcidin ameliorates anemia of chronic kidney disease in a mouse model Open Access

• A hepcidin-binding peptide we identified interferes with hepcidin-mediated ferroportin internalization and cellular iron accumulation.

• In an animal model of chronic kidney disease, the administration of hepcidin-binding peptide improved iron and hematologic parameter.

Iron plays a vital role in hematopoiesis and cellular metabolism as an essential constituent of hemoglobin, myoglobin and several other proteins. Systemic iron homeostasis is regulated by a peptide hormone, hepcidin. Hepcidin binds to a cellular iron exporter, ferroportin to induce its internalization and degradation, thereby reducing iron release from the iron-storage tissues to control the serum iron level. In chronic inflammatory conditions, excessive hepcidin expression is commonly observed. Excess hepcidin inappropriately promotes ferroportin degradation to reduce serum iron level and restricts iron availability for hemoglobin production. This contributes to the anemia of chronic diseases including chronic kidney disease. Therefore, inhibition of excess hepcidin activity can be a novel therapeutic approach for the treatment of anemia of chronic diseases. Here we identified a hepcidin-binding peptide (HBP) that functions as a hepcidin inhibitor by a phage display selection. We demonstrated that HBP inhibits the hepcidin-ferroportin interaction to neutralize excess hepcidin, resulting in increased release of iron from cellular storage in the in vitro and in vivo systems. Furthermore, HBP ameliorated anemia of chronic kidney disease by neutralizing excess hepcidin in an animal model. We thus presented HBP as a potential therapeutic agent for the treatment of anemia of chronic kidney disease.