Erythropoietin (Epo) is an indispensable erythropoietic
hormone primarily produced from renal Epo-producing cells (REPs). Epo production in REPs is tightly regulated in a
hypoxia-inducible manner to maintain tissue
oxygen homeostasis. Insufficient Epo production by REPs causes renal
anemia and
anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic
hypoxia-responsive cells to dynamic fibrogenic cells. In
chronic kidney disease, REPs are the major source of
scar-forming myofibroblasts and actively produce fibrogenic molecules, including inflammatory
cytokines. Notably, myofibroblast-transformed REPs (MF-REPs) recover their original physiological properties after resolution of the disease insults, suggesting that renal
anemia and
fibrosis could be reversible to some extent. Therefore, understanding the plasticity of REPs will lead to the development of novel targeted
therapeutics for both renal
fibrosis and
anemia. This review summarizes the regulatory mechanisms how
hypoxia-inducible Epo gene expression is attained in health and disease conditions.