气候变化领域集成服务门户(CCPortal): Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury

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DOI	10.1073/pnas.2022841118
	Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury
	Radhakrishnan K.; Kim Y.-H.; Jung Y.S.; Kim D.-K.; Na S.-Y.; Lim D.; Kim D.H.; Kim J.; Kim H.-S.; Choy H.E.; Cho S.J.; Lee I.-K.; Ayvaz Ş.; Nittka S.; Fliser D.; Schunk S.J.; Speer T.; Dooley S.; Lee C.-H.; Choi H.-S.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified. For insight, we investigated folic acid (FA)-induced AKI in mice. Interestingly, simultaneous with FGF23, orphan nuclear receptor ERR-γ expression is increased in the liver of FA-treated mice, and ectopic overexpression of ERR-γ was sufficient to induce hepatic FGF23 production. In patients and in mice, AKI is accompanied by up-regulated systemic IL-6, which was previously identified as an upstream regulator of ERR-γ expression in the liver. Administration of IL-6 neutralizing antibody to FA-treated mice or of recombinant IL-6 to healthy mice confirms IL-6 as an upstream regulator of hepatic ERR-γ-mediated FGF23 production. A significant (P < 0.001) interconnection between high IL-6 and FGF23 levels as a predictor of AKI in patients that underwent cardiac surgery was also found, suggesting the clinical relevance of the finding. Finally, liver-specific depletion of ERR-γ or treatment with an inverse ERR-γ agonist decreased hepatic FGF23 expression and plasma FGF23 levels in mice with FA-induced AKI. Thus, inverse agonist of ERR-γ may represent a therapeutic strategy to reduce adverse plasma FGF23 levels in AKI. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acute kidney injury; ERR-γ; FGF23; Interleukin 6; Orphan nuclear receptor
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179806
作者单位	School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, South Korea; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea; Department of Functional Genomics, Korea Research Institute of Biosciences and Biotechnology, School of Bioscience, University of Science and Technology, Daejeon, 34141, South Korea; Department of Molecular Biotechnology, Chonnam National University, Gwangju, 61186, South Korea; Department of Microbiology, Chonnam National University, Medical School, Gwangju, 61468, South Korea; Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, 41404, South Korea; New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu, 41061, South Korea; Department of Forensic Medicine, Chonnam National University, Medical School, Gwangju, 61468, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Di...
推荐引用方式 GB/T 7714	Radhakrishnan K.,Kim Y.-H.,Jung Y.S.,et al. Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury[J],2021,118(16).
APA	Radhakrishnan K..,Kim Y.-H..,Jung Y.S..,Kim D.-K..,Na S.-Y..,...&Choi H.-S..(2021).Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Radhakrishnan K.,et al."Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).