title: Renal erythropoietin-producing cells in health and disease.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine Sendai, Japan ; Division of Interdisciplinary Medical Science, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine Sendai, Japan ; Division of Nephrology and Hypertension, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Souma
authors.affiliation: Division of Interdisciplinary Medical Science, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine Sendai, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
keywords: erythropoietin; fibrosis; hypoxia; plasticity; renal Epo-producing cell (REP)