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Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells.
- Source :
- Scientific Reports; 2/16/2021, Vol. 11 Issue 1, p1-12, 12p
- Publication Year :
- 2021
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- TRETINOIN
ERYTHROPOIETIN
HYPOXEMIA
CHRONIC kidney failure
RENAL anemia
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- 148783181
- Full Text :
- https://doi.org/10.1038/s41598-021-83431-6