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

Autores
Li, Weizu; Ding, Yanfeng; Smedley, Crystal; Wang, Yanxia; Chaudhari, Sarika; Birnbaumer, Lutz; Ma, Rong
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Li, Weizu. Anhui Medical University; China
Fil: Ding, Yanfeng. University of North Texas; Estados Unidos
Fil: Smedley, Crystal. University of North Texas; Estados Unidos
Fil: Wang, Yanxia. University of North Texas; Estados Unidos
Fil: Chaudhari, Sarika. University of North Texas; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. National Institutes of Health; Estados Unidos
Fil: Ma, Rong. University of North Texas; Estados Unidos
Materia
TRPC
Kidney
Glomerular Filtration
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/49473
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout miceLi, WeizuDing, YanfengSmedley, CrystalWang, YanxiaChaudhari, SarikaBirnbaumer, LutzMa, RongTRPCKidneyGlomerular Filtrationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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.Fil: Li, Weizu. Anhui Medical University; ChinaFil: Ding, Yanfeng. University of North Texas; Estados UnidosFil: Smedley, Crystal. University of North Texas; Estados UnidosFil: Wang, Yanxia. University of North Texas; Estados UnidosFil: Chaudhari, Sarika. University of North Texas; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. National Institutes of Health; Estados UnidosFil: Ma, Rong. University of North Texas; Estados UnidosNature Publishing Group2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49473Li, Weizu; Ding, Yanfeng; Smedley, Crystal; Wang, Yanxia; Chaudhari, Sarika; et al.; Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice; Nature Publishing Group; Scientific Reports; 7; 1; 12-2017; 1-15; 41452045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-04067-zinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-04067-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:27Zoai:ri.conicet.gov.ar:11336/49473instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:09:27.403CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
title Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
spellingShingle Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
Li, Weizu
TRPC
Kidney
Glomerular Filtration
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
dc.creator.none.fl_str_mv Li, Weizu
Ding, Yanfeng
Smedley, Crystal
Wang, Yanxia
Chaudhari, Sarika
Birnbaumer, Lutz
Ma, Rong
author Li, Weizu
author_facet Li, Weizu
Ding, Yanfeng
Smedley, Crystal
Wang, Yanxia
Chaudhari, Sarika
Birnbaumer, Lutz
Ma, Rong
author_role author
author2 Ding, Yanfeng
Smedley, Crystal
Wang, Yanxia
Chaudhari, Sarika
Birnbaumer, Lutz
Ma, Rong
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC
Kidney
Glomerular Filtration
topic TRPC
Kidney
Glomerular Filtration
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Li, Weizu. Anhui Medical University; China
Fil: Ding, Yanfeng. University of North Texas; Estados Unidos
Fil: Smedley, Crystal. University of North Texas; Estados Unidos
Fil: Wang, Yanxia. University of North Texas; Estados Unidos
Fil: Chaudhari, Sarika. University of North Texas; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. National Institutes of Health; Estados Unidos
Fil: Ma, Rong. University of North Texas; Estados Unidos
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/49473
Li, Weizu; Ding, Yanfeng; Smedley, Crystal; Wang, Yanxia; Chaudhari, Sarika; et al.; Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice; Nature Publishing Group; Scientific Reports; 7; 1; 12-2017; 1-15; 4145
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49473
identifier_str_mv Li, Weizu; Ding, Yanfeng; Smedley, Crystal; Wang, Yanxia; Chaudhari, Sarika; et al.; Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice; Nature Publishing Group; Scientific Reports; 7; 1; 12-2017; 1-15; 4145
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-04067-z
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-04067-z
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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