Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice

Abstract The present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of...

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Autores principales:	Weizu Li, Yanfeng Ding, Crystal Smedley, Yanxia Wang, Sarika Chaudhari, Lutz Birnbaumer, Rong Ma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e7482ebd6724f61a2a0139a35c905f1
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spelling	oai:doaj.org-article:3e7482ebd6724f61a2a0139a35c905f12021-12-02T12:30:27ZIncreased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice10.1038/s41598-017-04067-z2045-2322https://doaj.org/article/3e7482ebd6724f61a2a0139a35c905f12017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04067-zhttps://doaj.org/toc/2045-2322Abstract The present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We found that GFR was significantly greater, and serum creatinine level was significantly lower in TRPC6 deficient mice. Consistently, local knockdown of TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang II-induced GFR decline in rats. Furthermore, Ang II-stimulated contraction and Ca2+ entry were significantly suppressed in primary MCs isolated from TRPC6 deficient mice, and the Ca2+ response could be rescued by re-introducing TRPC6. Moreover, inhibition of reverse mode of Na+-Ca2+ exchange by KB-R7943 significantly reduced Ca2+ entry response in TRPC6-expressing, but not in TRPC6-knocked down MCs. Ca2+ entry response was also significantly attenuated in Na+ free solution. Single knockdown of TRPC6 and TRPC1 resulted in a comparable suppression on Ca2+ entry with double knockdown of both. These results suggest that TRPC6 may regulate GFR by modulating MC contractile function through multiple Ca2+ signaling pathways.Weizu LiYanfeng DingCrystal SmedleyYanxia WangSarika ChaudhariLutz BirnbaumerRong MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Weizu Li Yanfeng Ding Crystal Smedley Yanxia Wang Sarika Chaudhari Lutz Birnbaumer Rong Ma Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
description	Abstract The present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We found that GFR was significantly greater, and serum creatinine level was significantly lower in TRPC6 deficient mice. Consistently, local knockdown of TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang II-induced GFR decline in rats. Furthermore, Ang II-stimulated contraction and Ca2+ entry were significantly suppressed in primary MCs isolated from TRPC6 deficient mice, and the Ca2+ response could be rescued by re-introducing TRPC6. Moreover, inhibition of reverse mode of Na+-Ca2+ exchange by KB-R7943 significantly reduced Ca2+ entry response in TRPC6-expressing, but not in TRPC6-knocked down MCs. Ca2+ entry response was also significantly attenuated in Na+ free solution. Single knockdown of TRPC6 and TRPC1 resulted in a comparable suppression on Ca2+ entry with double knockdown of both. These results suggest that TRPC6 may regulate GFR by modulating MC contractile function through multiple Ca2+ signaling pathways.
format	article
author	Weizu Li Yanfeng Ding Crystal Smedley Yanxia Wang Sarika Chaudhari Lutz Birnbaumer Rong Ma
author_facet	Weizu Li Yanfeng Ding Crystal Smedley Yanxia Wang Sarika Chaudhari Lutz Birnbaumer Rong Ma
author_sort	Weizu Li
title	Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
title_short	Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
title_full	Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
title_fullStr	Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
title_full_unstemmed	Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
title_sort	increased glomerular filtration rate and impaired contractile function of mesangial cells in trpc6 knockout mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3e7482ebd6724f61a2a0139a35c905f1
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Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice

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