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Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification in the absence of Klotho deficiency.

Abstract：

:Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that acts primarily on the kidney and parathyroid. With declining kidney function there is an increase in circulating FGF23 levels, which is associated with vascular calcification and mortality in chronic kidney disease. Whether FGF23 exerts direct effects on vasculature is unclear. We evaluated the expression of Klotho and FGF receptors in rat aortic rings and rat aorta vascular smooth muscle cells maintained in culture by reverse transcription-PCR, western blotting, and immunostaining. Signaling pathways underlying FGF23 effects were assessed by western blotting, and effects of FGF23 on osteogenic markers and phosphate transporters were assessed by real-time reverse transcription-PCR. We detected Klotho and FGFR1 in total aorta but not in vascular smooth muscle cells. FGF23 augmented phosphate-induced vascular calcification in the aortic rings from uremic rats and dose dependently increased ERK1/2 phosphorylation in Klotho-overexpressing but not naive vascular smooth muscle cells. FGF23-induced ERK1/2 phosphorylation was inhibited by SU5402 (FGFR1 inhibitor) and U0126 (MEK inhibitor). FGF23 enhanced phosphate-induced calcification in Klotho-overexpressing vascular smooth muscle cells and increased osteoblastic marker expression, which was inhibited by U0126. In contrast, phosphate transporter expression was not affected by phosphate or FGF23. Thus, FGF23 enhances phosphate-induced vascular calcification by promoting osteoblastic differentiation involving the ERK1/2 pathway.

journal_name

Kidney Int

journal_title

Kidney international

authors

Jimbo R,Kawakami-Mori F,Mu S,Hirohama D,Majtan B,Shimizu Y,Yatomi Y,Fukumoto S,Fujita T,Shimosawa T

doi

10.1038/ki.2013.332

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

1103-11

issue

5

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)56305-9

journal_volume

85

pub_type

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