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タイトル: | Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells |
著者: | Katagiri, Naoko Hitomi, Hirofumi Mae, Shin-Ichi Kotaka, Maki Lei, Li Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Nishiyama, Akira Osafune, Kenji https://orcid.org/0000-0001-7238-2763 (unconfirmed) |
著者名の別形: | 片桐, 直子 人見, 浩史 前, 伸一 小髙, 真希 山本, 拓也 西山, 成 長船, 健二 |
キーワード: | Regeneration Stem cells |
発行日: | 16-Feb-2021 |
出版者: | Springer Nature |
誌名: | Scientific Reports |
巻: | 11 |
論文番号: | 3936 |
抄録: | 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. |
著作権等: | © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
URI: | http://hdl.handle.net/2433/261734 |
DOI(出版社版): | 10.1038/s41598-021-83431-6 |
PubMed ID: | 33594180 |
出現コレクション: | 学術雑誌掲載論文等 |
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