fg-4592 and Kidney-Diseases

Topics: Anemia; Animals; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Kidney Diseases; Mice; Mice, Inbred C57BL; Procollagen-Proline Dioxygenase; Prolyl-Hydroxylase Inhibitors; Pyridines

We investigated the effect of roxadustat on factors associated with renal fibrosis and efficacy. After giving roxadustat, it can change the expression of HIF-1

Topics: Anemia; Fibrosis; Glycine; Hemoglobins; Hepcidins; Humans; Isoquinolines; Kidney Diseases; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

Erythropoietin (EPO) is a crucial hormone for erythropoiesis and produced by adult kidneys. Insufficient EPO production in chronic kidney disease (CKD) can cause renal anemia. Although hypoxia-inducible factors (HIFs) are known as a main regulator, the mechanisms of EPO production have not been fully elucidated. In this study, we aimed to examine the roles of retinoic acid (RA) in EPO production using EPO-producing cells derived from human induced pluripotent stem cells (hiPSC-EPO cells) that we previously established. RA augmented EPO production by hiPSC-EPO cells under hypoxia or by treatment with prolyl hydroxylase domain-containing protein (PHD) inhibitors that upregulate HIF signals. Combination treatment with RA and a PHD inhibitor improved renal anemia in vitamin A-depleted CKD model mice. Our findings using hiPSC-EPO cells and CKD model mice may contribute to clarifying the EPO production mechanism and developing efficient therapies for renal anemia.

Topics: Anemia; Animals; Basic Helix-Loop-Helix Transcription Factors; Drug Evaluation, Preclinical; Drug Therapy, Combination; Erythropoietin; Glycine; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Induced Pluripotent Stem Cells; Isoquinolines; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Tretinoin