Physiology and pathophysiology of renal erythropoietin-producing cells
Journal
Journal of the Formosan Medical Association
Journal Volume
117
Journal Issue
11
Pages
955-963
Date Issued
2018
Author(s)
Abstract
Anemia is a common complication and contributes to increased morbidity and mortality in chronic kidney disease (CKD) patients. Whereas there has been a significant improvement of understanding the underlying mechanism of erythropoiesis, the treatment of renal anemia is still restricted to erythropoietin (EPO)-stimulating agents. The purpose of this article is to review the physiology of erythropoiesis, functional role of EPO and underlying molecular and cellular basis that regulate EPO production. Regulation of EPO production is at mRNA level. When anemia or hypoxia occurs, transcriptional factor, hypoxia-inducible factor (HIF), binds to EPO 5′ hypoxic response element and EPO gene transcription increases. The renal EPO is mainly produced by pericytes. In CKD, pericytes transdifferentiate to myofibroblasts, and subsequently the ability of EPO production decreases, leading to renal anemia. Recent experimental and clinical studies show the promising efficacy of prolyl hydroxylase inhibitors in renal anemia through increasing EPO production by stabilizing HIF. Recent advances on epigenetics create a new field to study EPO gene expression at chromatin level. We will discuss the role of demethylating agent on restoring EPO expression, providing a novel approach to the treatment of renal anemia. ? 2018
Subjects
Chronic kidney disease; Epigenetics; Erythropoietin; Hypoxia-inducible factor; Myofibroblast; Pericyte
SDGs
Other Subjects
erythropoietin; hypoxia inducible factor; messenger RNA; prolyl hydroxylase inhibitor; transcription factor; EPO protein, human; erythropoietin; hypoxia inducible factor 1; anemia; burst forming unit E; cell transdifferentiation; chromatin; chronic kidney failure; epigenetics; erythropoiesis; gene control; gene expression; genetic transcription; human; hypoxia; kidney cell; molecular docking; myofibroblast; nonhuman; oxygen sensing; pathophysiology; pericyte; physiology; renal anemia; renal erythropoietin producing cell; Review; anemia; animal; complication; gene expression regulation; genetics; metabolism; Anemia; Animals; Erythropoiesis; Erythropoietin; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1; Myofibroblasts; Pericytes; Renal Insufficiency, Chronic
Publisher
Elsevier B.V.
Type
review