Authors: Michiko Hori Yuka Kinoshita Manabu Taguchi Seiji Fukumoto
Publish Date: 2015/03/21
Volume: 34, Issue: 2, Pages: 132-139
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 UMR106 which has been shown to express Fgf23 in response to 125dihydroxyvitamin D 125OH2D Phosphate increased Fgf23 expression in a dose and timedependent manner in the presence of 125OH2D Phosphate also increased Fgf23 promoter activity but showed no effect on the halflife 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 UMR106 cells and hydrogen peroxide enhanced FGF23 production in a dose and timedependent manner Hydrogen peroxide also enhanced Elk1 reporter activity a target of the MEK–extracellularsignalregulated 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 that phosphate directly enhances Fgf23 transcription without affecting the stability of Fgf23 messenger RNA by stimulating NADPHinduced ROS production and the MEK–ERK pathway in UMR106 cells
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