FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate

Ann E. Bowe, Richard Finnegan, Suzanne M Jan De Beur, Justin Cho, Michael A. Levine, Rajiv Kumar, Susan C. Schiavi

Research output: Contribution to journalArticle

Abstract

Oncogenic osteomalacia (OOM), X-linked hypophosphatemia (XLH), and autosomal dominant hypophosphatemic rickets (ADHR) are phenotypically similar disorders characterized by hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum calcitriol concentrations, normal serum concentrations of calcium and parathyroid hormone, and defective skeletal mineralization. XLH results from mutations in the PHEX gene, encoding a membrane-bound endopeptidase, whereas ADHR is associated with mutations of the gene encoding FGF-23. Recent evidence that FGF-23 is expressed in mesenchymal tumors associated with OOM suggests that FGF-23 is responsible for the phosphaturic activity previously termed "phosphatonin." Here we show that both wild-type FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells. We further show that the endopeptidase, PHEX, degrades native FGF-23 but not the mutant form. Our results suggest that FGF-23 is involved in the pathogenesis of these three hypophosphatemic disorders and directly link PHEX and FGF-23 within the same biochemical pathway.

Original languageEnglish (US)
Pages (from-to)977-981
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume284
Issue number4
DOIs
StatePublished - 2001

Fingerprint

Familial Hypophosphatemic Rickets
Endopeptidases
Gene encoding
Phosphates
Kidney
Calcitriol
Substrates
Parathyroid Hormone
Hypophosphatemia
Tumors
Mutation
Calcium
Membranes
Serum
Genes
Epithelial Cells
Autosomal Dominant Hypophosphatemic Rickets
Neoplasms
Oncogenic osteomalacia

Keywords

  • ADHR
  • FGF-23
  • Hypophosphatemia
  • OOM
  • Osteomalacia
  • PHEX
  • Phosphatonin
  • Rickets
  • XLH

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. / Bowe, Ann E.; Finnegan, Richard; Jan De Beur, Suzanne M; Cho, Justin; Levine, Michael A.; Kumar, Rajiv; Schiavi, Susan C.

In: Biochemical and Biophysical Research Communications, Vol. 284, No. 4, 2001, p. 977-981.

Research output: Contribution to journalArticle

Bowe, Ann E. ; Finnegan, Richard ; Jan De Beur, Suzanne M ; Cho, Justin ; Levine, Michael A. ; Kumar, Rajiv ; Schiavi, Susan C. / FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 284, No. 4. pp. 977-981.
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