{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T18:45:13Z","timestamp":1773168313679,"version":"3.50.1"},"reference-count":40,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:p>Fibroblast growth factor-23 (FGF-23) has been implicated in the renal phosphate wasting in X-linked hypophosphatemia, tumor-induced osteomalacia, and autosomal dominant hypophosphatemic rickets. Recently, we demonstrated that Hyp mice have greater urinary PGE<jats:sub>2<\/jats:sub>levels compared with C57\/B6 mice and that indomethacin administration in vivo and in vitro ameliorates the phosphate transport defect in Hyp mice. To determine further whether altered prostaglandin metabolism plays a role in the renal phosphate transport defect in Hyp mice, we incubated renal proximal tubules with arachidonic acid. We find that PGE<jats:sub>2<\/jats:sub>production was higher in Hyp mice than in C57\/B6 mice. Incubation of C57\/B6 mouse renal proximal tubules with FGF-23R176Q, an active mutant form of FGR23, increased tubular PGE<jats:sub>2<\/jats:sub>production, an effect that was inhibited by 50 \u03bcM PD-98059 and 10 \u03bcM SB-203580, inhibitors of the MAP kinase pathway. C57\/B6 mice injected with FGF-23R176Q had a \u223c10-fold increase in PGE<jats:sub>2<\/jats:sub>excretion 24 h after intraperitoneal injection of FGF-23R176Q compared with vehicle-treated controls. Finally, we show that PGE<jats:sub>2<\/jats:sub>inhibited both phosphate and volume absorption in mouse proximal convoluted tubules perfused in vitro and reduced brush-border membrane vesicle NaPi-2a protein abundance from renal cortex incubated in vitro with PGE<jats:sub>2<\/jats:sub>. In conclusion, FGF-23 increases urinary and renal tubular PGE<jats:sub>2<\/jats:sub>production via the MAP kinase pathway and PGE<jats:sub>2<\/jats:sub>inhibits proximal tubule phosphate transport.<\/jats:p>","DOI":"10.1152\/ajprenal.00234.2005","type":"journal-article","created":{"date-parts":[[2005,9,7]],"date-time":"2005-09-07T00:34:57Z","timestamp":1126053297000},"page":"F450-F455","source":"Crossref","is-referenced-by-count":13,"title":["Fibroblast growth factor-23 increases mouse PGE<sub>2<\/sub>production in vivo and in 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