EPO and HMGB1 signaling in erythroblasts. (Left) The normal condition. EPO interacts with its receptor and transduces a signal to STAT5, which activates erythroid genes. (Right) A model of anemia of inflammation. HMGB1 competes with EPO for binding to the EPO receptor. This reduces STAT5 phosphorylation which reduces expression of erythroid genes. An open question is which erythroid genes are regulated by the HMGB1/RAGE signaling pathway.