Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model

Abstract Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to...

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Autores principales:	Héloïse Bilbault, Joëlle Perez, Léa Huguet, Sophie Vandermeersch, Sandrine Placier, Nahid Tabibzadeh, Vincent Frochot, Emmanuel Letavernier, Dominique Bazin, Michel Daudon, Jean-Philippe Haymann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Urothelial Cell Proliferation Crystal Deposition FGF7 Groups FGF7 Administration Crystal Retention Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07d60bafadfa415b97acda90cb8c2494
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spelling	oai:doaj.org-article:07d60bafadfa415b97acda90cb8c24942021-12-02T15:09:06ZUrothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model10.1038/s41598-018-34734-82045-2322https://doaj.org/article/07d60bafadfa415b97acda90cb8c24942018-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34734-8https://doaj.org/toc/2045-2322Abstract Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.Héloïse BilbaultJoëlle PerezLéa HuguetSophie VandermeerschSandrine PlacierNahid TabibzadehVincent FrochotEmmanuel LetavernierDominique BazinMichel DaudonJean-Philippe HaymannNature PortfolioarticleUrothelial Cell ProliferationCrystal DepositionFGF7 GroupsFGF7 AdministrationCrystal RetentionMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Urothelial Cell Proliferation Crystal Deposition FGF7 Groups FGF7 Administration Crystal Retention Medicine R Science Q
spellingShingle	Urothelial Cell Proliferation Crystal Deposition FGF7 Groups FGF7 Administration Crystal Retention Medicine R Science Q Héloïse Bilbault Joëlle Perez Léa Huguet Sophie Vandermeersch Sandrine Placier Nahid Tabibzadeh Vincent Frochot Emmanuel Letavernier Dominique Bazin Michel Daudon Jean-Philippe Haymann Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
description	Abstract Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.
format	article
author	Héloïse Bilbault Joëlle Perez Léa Huguet Sophie Vandermeersch Sandrine Placier Nahid Tabibzadeh Vincent Frochot Emmanuel Letavernier Dominique Bazin Michel Daudon Jean-Philippe Haymann
author_facet	Héloïse Bilbault Joëlle Perez Léa Huguet Sophie Vandermeersch Sandrine Placier Nahid Tabibzadeh Vincent Frochot Emmanuel Letavernier Dominique Bazin Michel Daudon Jean-Philippe Haymann
author_sort	Héloïse Bilbault
title	Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
title_short	Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
title_full	Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
title_fullStr	Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
title_full_unstemmed	Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
title_sort	urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/07d60bafadfa415b97acda90cb8c2494
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_version_	1718387917358891008

Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model

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