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FGFR4 does not contribute to progression of chronic kidney disease.

Publication ,  Journal Article
Taylor, A; Yanucil, C; Musgrove, J; Shi, M; Ide, S; Souma, T; Faul, C; Wolf, M; Grabner, A
Published in: Sci Rep
October 1, 2019

In chronic kidney disease (CKD), elevated serum levels of the phosphate regulating hormone fibroblast growth factor (FGF) 23 have emerged as powerful risk factors for cardiovascular disease and death. Mechanistically, FGF23 can bind and activate fibroblast growth factor receptor (FGFR) 4 independently of α-klotho, the canonical co-receptor for FGF23 in the kidney, which stimulates left ventricular hypertrophy and hepatic production of inflammatory cytokines. FGF23 has also been shown to independently predict progression of renal disease, however, whether FGF23 and FGFR4 also contribute to CKD remains unknown. Here, we generated a mouse model with dual deletions of FGFR4 and α-klotho, and we induced CKD in mice with either global deletion or constitutive activation of FGFR4. We demonstrate that FGF23 is not capable of inducing phosphaturia via FGFR4 and that FGFR4 does not promote or mitigate renal injury in animal models of CKD. Taken together our results suggest FGFR4 inhibition as a safe alternative strategy to target cardiovascular disease and chronic inflammation in patients with CKD without interrupting the necessary phosphaturic effects of FGF23.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 1, 2019

Volume

9

Issue

1

Start / End Page

14023

Location

England

Related Subject Headings

  • Risk Factors
  • Renal Insufficiency, Chronic
  • Receptor, Fibroblast Growth Factor, Type 4
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Klotho Proteins
  • Humans
  • Glucuronidase
  • Gene Knock-In Techniques
 

Citation

APA
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Taylor, A., Yanucil, C., Musgrove, J., Shi, M., Ide, S., Souma, T., … Grabner, A. (2019). FGFR4 does not contribute to progression of chronic kidney disease. Sci Rep, 9(1), 14023. https://doi.org/10.1038/s41598-019-50669-0
Taylor, Ashlee, Christopher Yanucil, John Musgrove, Melody Shi, Shintaro Ide, Tomokazu Souma, Christian Faul, Myles Wolf, and Alexander Grabner. “FGFR4 does not contribute to progression of chronic kidney disease.Sci Rep 9, no. 1 (October 1, 2019): 14023. https://doi.org/10.1038/s41598-019-50669-0.
Taylor A, Yanucil C, Musgrove J, Shi M, Ide S, Souma T, et al. FGFR4 does not contribute to progression of chronic kidney disease. Sci Rep. 2019 Oct 1;9(1):14023.
Taylor, Ashlee, et al. “FGFR4 does not contribute to progression of chronic kidney disease.Sci Rep, vol. 9, no. 1, Oct. 2019, p. 14023. Pubmed, doi:10.1038/s41598-019-50669-0.
Taylor A, Yanucil C, Musgrove J, Shi M, Ide S, Souma T, Faul C, Wolf M, Grabner A. FGFR4 does not contribute to progression of chronic kidney disease. Sci Rep. 2019 Oct 1;9(1):14023.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 1, 2019

Volume

9

Issue

1

Start / End Page

14023

Location

England

Related Subject Headings

  • Risk Factors
  • Renal Insufficiency, Chronic
  • Receptor, Fibroblast Growth Factor, Type 4
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Klotho Proteins
  • Humans
  • Glucuronidase
  • Gene Knock-In Techniques