FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts

@article{Smith2017FGF23IS,
  title={FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts},
  author={Edward R. Smith and Sven‐Jean Tan and Stephen G. Holt and Tim D. Hewitson},
  journal={Scientific Reports},
  year={2017},
  volume={7}
}
In kidney disease, higher circulating levels of the mineral-regulating hormone fibroblast growth factor (FGF)-23 are predictive of disease progression but direct pathogenic effects on the kidney are unknown. We sought evidence of local renal synthesis in response to unilateral ureteric obstruction in the mouse, and pro-fibrotic actions of FGF23 on the fibroblast in vitro. Acute tubulointerstitial injury due to unilateral ureteric obstruction stimulated renal FGF23 synthesis by tubules, and… Expand
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References

SHOWING 1-10 OF 73 REFERENCES
Key role of the kidney in the regulation of fibroblast growth factor 23.
TLDR
The kidney is important in FGF23 homeostasis by regulation of its plasma level and metabolism in acute uremia as induced by bilateral or unilateral nephrectomy in the rat. Expand
Plasma FGF23 levels increase rapidly after acute kidney injury
Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs we used aExpand
A Comparative Transcriptome Analysis Identifying FGF23 Regulated Genes in the Kidney of a Mouse CKD Model
TLDR
A comparative genome wide analysis of gene expression profiles in the kidney of the Collagen 4 alpha 3 null mice model of progressive kidney disease found that α-Klotho, an anti-aging hormone and FGF23 co-receptor, was decreased by F GF23, thereby providing a pathway for FGF 23 regulation of the renin-angiotensin system. Expand
Renal Expression of FGF23 in Progressive Renal Disease of Diabetes and the Effect of Ace Inhibitor
TLDR
The data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition, and interfering pharmacologically with the delicate balance of F GF23 and phosphorus in diabetes may have implications in clinics. Expand
Renal expression of FGF23 and peripheral resistance to elevated FGF23 in rodent models of polycystic kidney disease.
TLDR
The polycystic kidney produces FGF23 but is resistant to its action, as shown in rats with PKD and in an inducible Pkd1 knockout mouse model. Expand
Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production
TLDR
Simultaneous upregulation of F GF23 cleavage in osteocytes maintains near-normal levels of biologically active, intact circulating FGF23, whereas downregulated or impaired FGF24 cleavage may contribute to elevated intact serum FGF 23 in CKD. Expand
Interleukin-1-induced acute bone resorption facilitates the secretion of fibroblast growth factor 23 into the circulation
TLDR
The hypothesis that osteoclastic bone resorption may play a role in regulating circulating levels of FGF23 is tested using a mouse model where injections of interleukin into the subcutaneous tissue over the calvaria induced rapid bone Resorption. Expand
Fibroblast growth factor 23 modifies the pharmacological effects of angiotensin receptor blockade in experimental renal fibrosis
  • M. D. de Jong, K. Mirković, +7 authors M. D. de Borst
  • Medicine
  • Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2017
TLDR
These findings show pharmacological interaction between exogenous FGF23 and losartan, thus serving as a proof of principle for crosstalk between the F GF23–klotho axis and RAAS. Expand
Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy.
TLDR
It is reported that FGF23 exclusively activates FGFR4 on cardiac myocytes to stimulate phospholipase Cγ/calcineurin/nuclear factor of activated T cell signaling and promotes LVH by activatingFGFR4, thereby establishing FGFR 4 as a pharmacological target for reducing cardiovascular risk in CKD. Expand
Longitudinal evaluation of FGF23 changes and mineral metabolism abnormalities in a mouse model of chronic kidney disease
  • Jason R. Stubbs, Nan He, +5 authors L. Quarles
  • Biology, Medicine
  • Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2012
TLDR
Elevations of FGF23 in CKD are suggested to be an early marker of renal injury that increases before BUN and serum creatinine and coincides with an increase in urinary phosphate excretion that likely prevents the early onset of hyperphosphatemia in the face of increased bone turnover and a progressive decline in functional renal mass. Expand
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