Crosstalk between Erythropoiesis and Iron Metabolism

Oxygen delivery is essential to sustain all vital functions. Vertebrate organisms have, therefore, evolved sophisticated and tightly regulated mechanisms to ensure continuous red cell synthesis. Chronic or acute blood losses trigger multiple feedback mechanisms aimed at increasing erythropoiesis and minimizing the damage associated with profound anemia and hypoxia. Iron is an element of paramount importance for ery-thropoiesis, being an essential part of the hemoglobin metalloprotein that ensures oxygen absorption, transport, and delivery. Therefore, it is not surprising that iron absorption and transport are closely linked to the demands of erythropoiesis. However, the mechanisms underlying this interconnected relationship have only recently started being understood. The focus of this special issue is on iron metabolism, erythropoiesis, and their close association, with a special emphasis on proteins regulating iron metabolism and how erythropoiesis affects their expression. The mechanistic view will be integrated with the clinical observations in disease such as myelodysplastic syndromes, sickle cell anemia, Diamond-Blackfan anemia, and anemia of inflammation. And finally, in light of these new discoveries, new potential therapies for well-known disorders such as beta-thalassemia will be discussed. In the last decade, new discoveries have fueled the field of iron metabolism. The papers Miller [4] provide a comprehensive and updated overview of the proteins involved in regulating dietary iron absorption, plasma iron concentrations, tissue iron distribution, and erythropoiesis. The review [1] introduces the mechanisms of crosstalk between iron and erythropoiesis and their function in different diseases. E. Nemeth [2] describes the role of the peptide hormone hepcidin in iron physiology and in many iron-related disorders and highlights the potential of hepcidin agonists and antagonist as future therapeutic tools for iron disorders. The paper by L. Cianetti et al. [3] describes the hepcidin receptor and iron transporter ferroportin and its role during normal and pathological erythroid differentiation. The paper by T. Tanno and J. L. Miller [4] describes the relationship between iron regulation and ineffective erythropoiesis, focusing on potential mechanisms for pathological iron overloading. Improved knowledge on proteins that interconnect iron metabolism and erythropoiesis is opening new prospective to develop new therapies, such as in beta-thalassemia. The review by L. Melchiori et al. [5] provides important evidence that use of Jak2 inhibitors or hepcidin agonists may ameliorate the abnormal erythropoiesis and iron overload in β-thalassemia. The interdependence of erythropoiesis and iron regulation extends beyond normal metabolism to include several pathological conditions. Diseases that are primarily associated with erythroid defects often lead …