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Sci Rep. 2017 Jun 13;7(1):3345. doi: 10.1038/s41598-017-02709-w.

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

Author information

1
Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia. edward.smith@mh.org.au.
2
Department of Medicine - Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia. edward.smith@mh.org.au.
3
Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
4
Department of Medicine - Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Abstract

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 downregulated inactivating proprotein convertases, without effects on systemic mineral metabolism. In vitro, FGF23 had divergent effects on fibroblast activation in cells derived from normal and obstructed kidneys. While FGF23 failed to stimulate fibrogenesis in normal fibroblasts, in those primed by injury, FGF23 induced pro-fibrotic signalling cascades via activation of TGF-β pathways. Effects were independent of α-klotho. Tubule-derived FGF23 may amplify myofibroblast activation in acute renal injury, and might provide a novel therapeutic target in renal fibrosis.

PMID:
28611350
PMCID:
PMC5469734
DOI:
10.1038/s41598-017-02709-w
[Indexed for MEDLINE]
Free PMC Article

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