A protective role for FGF-23 in local defence against disrupted arterial wall integrity?

Mol Cell Endocrinol. 2013 Jun 15;372(1-2):1-11. doi: 10.1016/j.mce.2013.03.008. Epub 2013 Mar 21.

Abstract

Increasing interest is focusing on the role of the FGF-23/Klotho axis in mediating vascular calcification. However, the underpinning mechanisms have yet to be fully elucidated. Murine VSMCs were cultured in calcifying medium for a 21 d period. FGF-23 mRNA expression was significantly up-regulated by 7d (1.63-fold; P<0.001), with a concomitant increase in protein expression. mRNA and protein expression of both FGFR1 and Klotho were confirmed. Increased FGF-23 and Klotho protein expression was also observed in the calcified media of Enpp1(-/-) mouse aortic tissue. Reduced calcium deposition was observed in calcifying VSMCs cultured with recombinant FGF-23 (10 ng/ml; 28.1% decrease; P<0.01). Calcifying VSMCs treated with PD173074, an inhibitor of FGFR1 and FGFR3, showed significantly increased calcification (50 nM; 87.8% increase; P<0.001). FGF-23 exposure induced phosphorylation of ERK1/2. Treatment with FGF-23 in combination with PD98059, an ERK1/2 inhibitor, significantly increased VSMC calcification (10 μM; 41.3% increase; P<0.01). Use of FGF-23 may represent a novel therapeutic strategy for inhibiting vascular calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / metabolism
  • Aorta / pathology*
  • Calcium / metabolism
  • Cell Survival
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / physiology*
  • Gene Expression
  • Gene Expression Regulation
  • Glucuronidase / genetics
  • Glucuronidase / metabolism
  • Klotho Proteins
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Primary Cell Culture
  • Pyrimidines / pharmacology
  • Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Vascular Calcification / metabolism

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Fgf23 protein, mouse
  • PD 173074
  • Pyrimidines
  • Runx2 protein, mouse
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Fgfr1 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
  • Glucuronidase
  • Klotho Proteins
  • Calcium