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

Dongxing Zhu, Neil C W Mackenzie, Jose Luis Millan, Colin Farquharson, Vicky E Macrae

Research output: Contribution to journalArticlepeer-review

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 7 d (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.
Original languageEnglish
Pages (from-to)1-11
JournalMolecular and Cellular Endocrinology
Volume372
Issue number1-2
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Vascular calcification
  • Vascular smooth muscle cells
  • Enpp1
  • FGF-23

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