Altered renal FGF23-mediated activity involving MAPK and Wnt

Effects of the Hyp mutation

Emily G. Farrow, Lelia J. Summers, Susan C. Schiavi, James (Jim) McCormick, David Ellison, Kenneth E. White

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Fibroblast growth factor-23 (FGF23), a hormone central to renal phosphate handling, is elevated in multiple hypophosphatemic disorders. Initial FGF23-dependent Erk1/2 activity in the kidney localizes to the distal convoluted tubule (DCT) with the co-receptor α-Klotho (KL), distinct from Npt2a in proximal tubules (PT). The Hyp mouse model of X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia with increased Fgf23, and patients with XLH elevate FGF23 following combination therapy of phosphate and calcitriol. The molecular signaling underlying renal FGF23 activity, and whether these pathways are altered in hypophosphatemic disorders, is unknown. To examine Npt2a in vivo, mice were injected with FGF23. Initial p-Erk1/2 activity in the DCT occurred within 10 min; however, Npt2a protein was latently reduced in the PT at 30-60 min, and was independent of Npt2a mRNA changes. KL-null mice had no DCT p-Erk1/2 staining following FGF23 delivery. Under basal conditions in Hyp mice, c-Fos and Egr1, markers of renal Fgf23 activity, were increased; however, KL mRNA was reduced 60% (P

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalJournal of Endocrinology
Volume207
Issue number1
DOIs
StatePublished - 2010

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Kidney
Mutation
Familial Hypophosphatemic Rickets
Phosphates
Hypophosphatemia
Messenger RNA
Calcitriol
fibroblast growth factor 23
Hormones
Staining and Labeling
Proteins
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Altered renal FGF23-mediated activity involving MAPK and Wnt : Effects of the Hyp mutation. / Farrow, Emily G.; Summers, Lelia J.; Schiavi, Susan C.; McCormick, James (Jim); Ellison, David; White, Kenneth E.

In: Journal of Endocrinology, Vol. 207, No. 1, 2010, p. 67-75.

Research output: Contribution to journalArticle

Farrow, Emily G. ; Summers, Lelia J. ; Schiavi, Susan C. ; McCormick, James (Jim) ; Ellison, David ; White, Kenneth E. / Altered renal FGF23-mediated activity involving MAPK and Wnt : Effects of the Hyp mutation. In: Journal of Endocrinology. 2010 ; Vol. 207, No. 1. pp. 67-75.
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