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

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 obst...

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Autores principales:	Edward R. Smith, Sven-Jean Tan, Stephen G. Holt, Tim D. Hewitson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa93e77520674b35bece2d357cb8d726
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spelling	oai:doaj.org-article:aa93e77520674b35bece2d357cb8d7262021-12-02T15:18:53ZFGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts10.1038/s41598-017-02709-w2045-2322https://doaj.org/article/aa93e77520674b35bece2d357cb8d7262017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02709-whttps://doaj.org/toc/2045-2322Abstract 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.Edward R. SmithSven-Jean TanStephen G. HoltTim D. HewitsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Edward R. Smith Sven-Jean Tan Stephen G. Holt Tim D. Hewitson FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
description	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.
format	article
author	Edward R. Smith Sven-Jean Tan Stephen G. Holt Tim D. Hewitson
author_facet	Edward R. Smith Sven-Jean Tan Stephen G. Holt Tim D. Hewitson
author_sort	Edward R. Smith
title	FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
title_short	FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
title_full	FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
title_fullStr	FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
title_full_unstemmed	FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
title_sort	fgf23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/aa93e77520674b35bece2d357cb8d726
work_keys_str_mv	AT edwardrsmith fgf23issynthesisedlocallybyrenaltubulesandactivatesinjuryprimedfibroblasts AT svenjeantan fgf23issynthesisedlocallybyrenaltubulesandactivatesinjuryprimedfibroblasts AT stephengholt fgf23issynthesisedlocallybyrenaltubulesandactivatesinjuryprimedfibroblasts AT timdhewitson fgf23issynthesisedlocallybyrenaltubulesandactivatesinjuryprimedfibroblasts
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FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts

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