Fibroblast growth factor (Fgf) 23 gene transcription depends on actin cytoskeleton reorganization

FEBS Lett. 2016 Mar;590(6):705-15. doi: 10.1002/1873-3468.12096. Epub 2016 Feb 27.

Abstract

FGF23 regulates renal phosphate and vitamin D metabolism. Loss of FGF23 results in massive calcification and rapid aging. FGF23 production is stimulated by 1,25(OH)2D3 and NFκB signaling. Here, we report that treatment of UMR106 osteoblast-like cells with 1,25(OH)2D3, inducing Fgf23 transcription, resulted in actin polymerization which was blocked by NFκB inhibitor wogonin. Interestingly, 1,25(OH)2D3-induced Fgf23 gene transcription was abolished by the actin microfilament-disrupting agent cytochalasin B, as well as by the inhibition of actin-regulating Rac1/PAK1 signaling. Our results provide strong evidence that actin redistribution regulated by the Rac1/PAK1 pathway participates in 1,25(OH)2D3-induced Fgf23 gene transcription.

Keywords: PAK1; Rac1; Vitamin D; actin polymerization; cytochalasin B; fibroblast growth factor 23.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism*
  • Animals
  • Calcitriol / metabolism
  • Calcitriol / pharmacology
  • Cell Line
  • Cytochalasin B / pharmacology
  • Fibroblast Growth Factors / biosynthesis
  • Fibroblast Growth Factors / genetics*
  • Flavanones / pharmacology
  • Microscopy, Confocal
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Fgf23 protein, rat
  • Flavanones
  • NF-kappa B
  • Cytochalasin B
  • Fibroblast Growth Factors
  • Pak1 protein, rat
  • p21-Activated Kinases
  • Rac1 protein, rat
  • rac1 GTP-Binding Protein
  • Calcitriol
  • wogonin