Phosphate enhances Fgf23 expression through reactive oxygen species in UMR-106 cells

Journal of Bone and Mineral Metabolism
Michiko HoriSeiji Fukumoto

Abstract

Fibroblast growth factor 23 (FGF23) has been shown to work as a phosphotropic hormone. Although FGF23 reduces the serum phosphate level, it has not been established that phosphate directly regulates FGF23 production. In this study, we investigated whether phosphate can enhance Fgf23 expression using the rat osteoblastic cell line UMR-106, which has been shown to express Fgf23 in response to 1,25-dihydroxyvitamin D [1,25(OH)2D]. Phosphate increased Fgf23 expression in a dose- and time-dependent manner in the presence of 1,25(OH)2D. Phosphate also increased Fgf23 promoter activity, but showed no effect on the half-life of Fgf23 messenger RNA. Phosphonoformic acid and PD98059, an inhibitor of MEK, inhibited the effects of phosphate on Fgf23 expression and promoter activity. In addition, phosphate enhanced production of reactive oxygen species (ROS) in UMR-106 cells, and hydrogen peroxide enhanced FGF23 production in a dose- and time-dependent manner. Hydrogen peroxide also enhanced Elk1 reporter activity, a target of the MEK-extracellular-signal-regulated kinase (ERK) pathway. Furthermore, the effect of phosphate on ROS production and Fgf23 expression was inhibited by apocynin, an inhibitor of NADPH oxidase. These results indicate...Continue Reading

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Citations

Jun 11, 2016·Kidney International·Hirotaka Komaba, Masafumi Fukagawa
Jan 29, 2017·Molecular Nutrition & Food Research·Ludmilla BärMichael Föller
Aug 6, 2017·Cold Spring Harbor Perspectives in Medicine·Marie Courbebaisse, Beate Lanske
Aug 16, 2018·Physiological Reviews·Toshimi MichigamiKeiichi Ozono
Sep 16, 2018·Nature Reviews. Endocrinology·Sampada Chande, Clemens Bergwitz
Dec 5, 2019·Journal of Bone and Mineral Metabolism·Seiji FukumotoToshio Matsumoto
Mar 20, 2020·Expert Opinion on Therapeutic Targets·Mario CozzolinoCarsten Alexander Wagner
May 20, 2020·Current Opinion in Nephrology and Hypertension·Yuichi Takashi, Seiji Fukumoto
Feb 28, 2019·Orphanet Journal of Rare Diseases·Signe Sparre Beck-NielsenOuti Mäkitie
May 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yuichi TakashiSeiji Fukumoto
May 22, 2018·International Journal of Endocrinology·Kenichi AkiyamaKazuhiro Shiizaki
Sep 29, 2020·Frontiers in Endocrinology·Rafiou AgoroKenneth E White
Apr 12, 2019·Frontiers in Endocrinology·Toshimi Michigami, Keiichi Ozono
Nov 26, 2020·International Journal of Molecular Sciences·Maria L MaceEwa Lewin
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Jun 3, 2021·Genes·Anna PapadopoulouFotini-Eleni Karachaliou
Jun 19, 2021·Frontiers in Cell and Developmental Biology·Xiaoyun LinHua Yue
Jul 3, 2021·Journal of Clinical Medicine·Javier Donate-CorreaJuan F Navarro-González
Aug 8, 2021·International Journal of Molecular Sciences·Marco Antonio Lacerda-Abreu, José Roberto Meyer-Fernandes

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