Initial FGF23-mediated signaling occurs in the distal convoluted tubule

Emily G. Farrow, Siobhan I. Davis, Lelia J. Summers, Kenneth E. White

Research output: Contribution to journalArticle

165 Scopus citations


Fibroblast growth factor-23 (FGF23), a hormone central to phosphate and vitamin D metabolism, reduces renal absorption of phosphate by downregulating the sodium-phosphate cotransporter Npt2a. However, the mechanisms of FGF23 action in the kidney are unclear, as Npt2a localizes to the proximal tubule (PT) and the FGF23 coreceptor α-Klotho (KL) localizes to the distal convoluted tubule (DCT). Immunofluorescent analyses following FGF23 injection in mice showed robust staining for phospho-ERK1/2, a marker of FGF23 bioactivity, only within the DCT in a subset of KL-positive cells. This activity colocalized with the FGF23 receptor FGFR1 and was present in DCT cells that were adjacent to Npt2a-expressing PT segments. Although KL is expressed as both secreted and membrane-bound isoforms, only the membrane-bound isoform was capable of mediating FGF23 bioactivity. These findings provide novel insight into the mechanisms of hormone-regulated phosphate metabolism by identifying an intrarenal signaling axis for FGF23.

Original languageEnglish (US)
Pages (from-to)955-960
Number of pages6
JournalJournal of the American Society of Nephrology
Issue number5
StatePublished - May 2009

ASJC Scopus subject areas

  • Nephrology

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