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Verfasst von:Radhakrishnan, Kamalakannan [VerfasserIn]   i
 Kim, Yong-Hoon [VerfasserIn]   i
 Jung, Yoon Seok [VerfasserIn]   i
 Kim, Don-Kyu [VerfasserIn]   i
 Na, Soon-Young [VerfasserIn]   i
 Lim, Daejin [VerfasserIn]   i
 Kim, Dong Hun [VerfasserIn]   i
 Kim, Jina [VerfasserIn]   i
 Kim, Hyung-Seok [VerfasserIn]   i
 Choy, Hyon E. [VerfasserIn]   i
 Cho, Sung Jin [VerfasserIn]   i
 Lee, In-Kyu [VerfasserIn]   i
 Ayvaz, Şamil [VerfasserIn]   i
 Nittka, Stefanie [VerfasserIn]   i
 Fliser, Danilo [VerfasserIn]   i
 Schunk, Stefan J. [VerfasserIn]   i
 Speer, Thimoteus [VerfasserIn]   i
 Dooley, Steven [VerfasserIn]   i
 Lee, Chul-Ho [VerfasserIn]   i
 Choi, Hueng-Sik [VerfasserIn]   i
Titel:Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury
Verf.angabe:Kamalakannan Radhakrishnan, Yong-Hoon Kim, Yoon Seok Jung, Don-Kyu Kim, Soon-Young Na, Daejin Lim, Dong Hun Kim, Jina Kim, Hyung-Seok Kim, Hyon E. Choy, Sung Jin Cho, In-Kyu Lee, Şamil Ayvaz, Stefanie Nittka, Danilo Fliser, Stefan J. Schunk, Thimoteus Speer, Steven Dooley, Chul-Ho Lee, and Hueng-Sik Choi
E-Jahr:2021
Jahr:April 20,2021
Umfang:11 S.
Fussnoten:Gesehen am 02.08.2021
Titel Quelle:Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
Ort Quelle:Washington, DC : National Acad. of Sciences, 1915
Jahr Quelle:2021
Band/Heft Quelle:118(2021), 16, Artikel-ID e2022841118, Seite 1-11
ISSN Quelle:1091-6490
Abstract: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.
DOI:doi:10.1073/pnas.2022841118
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1073/pnas.2022841118
 Volltext: https://www.pnas.org/content/118/16/e2022841118
 DOI: https://doi.org/10.1073/pnas.2022841118
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:acute kidney injury
 ERR-γ
 FGF23
 interleukin 6
 orphan nuclear receptor
K10plus-PPN:1765258057
Verknüpfungen:→ Zeitschrift

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