Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro

Ashu Syal, Susan Schiavi, Sumana Chakravarty, Vangipuram Dwarakanath, Raymond Quigley, Michel Baum

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 PGE2 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 2 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 PGE2 production, an effect that was inhibited by 50 μM PD-98059 and 10 μM SB-203580, inhibitors of the MAP kinase pathway. C57/B6 mice injected with FGF-23R176Q had a ∼10-fold increase in PGE2 excretion 24 h after intraperitoneal injection of FGF-23R176Q compared with vehicle-treated controls. Finally, we show that PGE2 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 2. In conclusion, FGF-23 increases urinary and renal tubular PGE 2 production via the MAP kinase pathway and PGE2 inhibits proximal tubule phosphate transport.

Original languageEnglish (US)
Pages (from-to)F450-F455
JournalAmerican Journal of Physiology - Renal Physiology
Volume290
Issue number2
DOIs
StatePublished - Feb 1 2006

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Keywords

  • In vitro microperfusion
  • NaPi-2a
  • Prostaglandin E
  • Rickets
  • Volume absorption

ASJC Scopus subject areas

  • Physiology
  • Urology

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