Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-83431-6 |
| _version_ | 1819127021033226240 |
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| author | Naoko Katagiri Hirofumi Hitomi Shin-Ichi Mae Maki Kotaka Li Lei Takuya Yamamoto Akira Nishiyama Kenji Osafune |
| author_facet | Naoko Katagiri Hirofumi Hitomi Shin-Ichi Mae Maki Kotaka Li Lei Takuya Yamamoto Akira Nishiyama Kenji Osafune |
| author_sort | Naoko Katagiri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T08:05:18Z |
| format | Article |
| id | doaj.art-fb684e94675646a998a711fcfd4223f2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T08:05:18Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fb684e94675646a998a711fcfd4223f22022-12-21T18:33:09ZengNature PortfolioScientific Reports2045-23222021-02-0111111210.1038/s41598-021-83431-6Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cellsNaoko Katagiri0Hirofumi Hitomi1Shin-Ichi Mae2Maki Kotaka3Li Lei4Takuya Yamamoto5Akira Nishiyama6Kenji Osafune7Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto UniversityDepartment of iPS Stem Cell Regenerative Medicine, Kansai Medical UniversityDepartment of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto UniversityDepartment of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto UniversityDepartment of Pharmacology, Faculty of Medicine, Kagawa UniversityDepartment of Life Science Frontiers, CiRA, Kyoto UniversityDepartment of Pharmacology, Faculty of Medicine, Kagawa UniversityDepartment of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto UniversityAbstract 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.https://doi.org/10.1038/s41598-021-83431-6 |
| spellingShingle | Naoko Katagiri Hirofumi Hitomi Shin-Ichi Mae Maki Kotaka Li Lei Takuya Yamamoto Akira Nishiyama Kenji Osafune Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells Scientific Reports |
| title | Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells |
| title_full | Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells |
| title_fullStr | Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells |
| title_full_unstemmed | Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells |
| title_short | Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells |
| title_sort | retinoic acid regulates erythropoietin production cooperatively with hypoxia inducible factors in human ipsc derived erythropoietin producing cells |
| url | https://doi.org/10.1038/s41598-021-83431-6 |
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