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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Autores principales:	Naoko Katagiri, Hirofumi Hitomi, Shin-Ichi Mae, Maki Kotaka, Li Lei, Takuya Yamamoto, Akira Nishiyama, Kenji Osafune
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb684e94675646a998a711fcfd4223f2
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spelling	oai:doaj.org-article:fb684e94675646a998a711fcfd4223f22021-12-02T10:54:30ZRetinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells10.1038/s41598-021-83431-62045-2322https://doaj.org/article/fb684e94675646a998a711fcfd4223f22021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83431-6https://doaj.org/toc/2045-2322Abstract 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.Naoko KatagiriHirofumi HitomiShin-Ichi MaeMaki KotakaLi LeiTakuya YamamotoAkira NishiyamaKenji OsafuneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human ipsc-derived erythropoietin-producing cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fb684e94675646a998a711fcfd4223f2
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Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells

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