Specific calpain inhibition protects kidney against inflammaging

Abstract Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that s...

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Autores principales:	Guillaume Hanouna, Laurent Mesnard, Sophie Vandermeersch, Joëlle Perez, Sandrine Placier, Jean-Philippe Haymann, Fabien Campagne, Julien Moroch, Aurélien Bataille, Laurent Baud, Emmanuel Letavernier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3860defad88411f8f61a846a295deea
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spelling	oai:doaj.org-article:f3860defad88411f8f61a846a295deea2021-12-02T15:05:44ZSpecific calpain inhibition protects kidney against inflammaging10.1038/s41598-017-07922-12045-2322https://doaj.org/article/f3860defad88411f8f61a846a295deea2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07922-1https://doaj.org/toc/2045-2322Abstract Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice. In addition, we analysed inflammatory response in the kidney of aged CalpTG and wild-type mice, and in both in vivo (monosodium urate peritonitis) and in vitro models of inflammation. At two years, CalpTG mice had preserved kidney tissue, less vascular remodelling and less markers of senescence than wild-type mice. Nevertheless, CalpTG mice lifespan was not extended, due to the development of lethal spleen tumors. Inflammatory pathways were less expressed in aged CalpTG mice, especially cytokines related to NF-κB and NLRP3 inflammasome activation. CalpTG mice had reduced macrophage infiltration with aging and CalpTG mice produced less IL-1α and IL-1β in vivo in response to inflammasome activators. In vitro, macrophages from CalpTG mice produced less IL-1α in response to particulate activators of inflammasome. Calpains inhibition protects against inflammaging, limiting kidney and vascular lesions related to aging.Guillaume HanounaLaurent MesnardSophie VandermeerschJoëlle PerezSandrine PlacierJean-Philippe HaymannFabien CampagneJulien MorochAurélien BatailleLaurent BaudEmmanuel LetavernierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guillaume Hanouna Laurent Mesnard Sophie Vandermeersch Joëlle Perez Sandrine Placier Jean-Philippe Haymann Fabien Campagne Julien Moroch Aurélien Bataille Laurent Baud Emmanuel Letavernier Specific calpain inhibition protects kidney against inflammaging
description	Abstract Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice. In addition, we analysed inflammatory response in the kidney of aged CalpTG and wild-type mice, and in both in vivo (monosodium urate peritonitis) and in vitro models of inflammation. At two years, CalpTG mice had preserved kidney tissue, less vascular remodelling and less markers of senescence than wild-type mice. Nevertheless, CalpTG mice lifespan was not extended, due to the development of lethal spleen tumors. Inflammatory pathways were less expressed in aged CalpTG mice, especially cytokines related to NF-κB and NLRP3 inflammasome activation. CalpTG mice had reduced macrophage infiltration with aging and CalpTG mice produced less IL-1α and IL-1β in vivo in response to inflammasome activators. In vitro, macrophages from CalpTG mice produced less IL-1α in response to particulate activators of inflammasome. Calpains inhibition protects against inflammaging, limiting kidney and vascular lesions related to aging.
format	article
author	Guillaume Hanouna Laurent Mesnard Sophie Vandermeersch Joëlle Perez Sandrine Placier Jean-Philippe Haymann Fabien Campagne Julien Moroch Aurélien Bataille Laurent Baud Emmanuel Letavernier
author_facet	Guillaume Hanouna Laurent Mesnard Sophie Vandermeersch Joëlle Perez Sandrine Placier Jean-Philippe Haymann Fabien Campagne Julien Moroch Aurélien Bataille Laurent Baud Emmanuel Letavernier
author_sort	Guillaume Hanouna
title	Specific calpain inhibition protects kidney against inflammaging
title_short	Specific calpain inhibition protects kidney against inflammaging
title_full	Specific calpain inhibition protects kidney against inflammaging
title_fullStr	Specific calpain inhibition protects kidney against inflammaging
title_full_unstemmed	Specific calpain inhibition protects kidney against inflammaging
title_sort	specific calpain inhibition protects kidney against inflammaging
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f3860defad88411f8f61a846a295deea
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Specific calpain inhibition protects kidney against inflammaging

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