Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway

Autores
Liu, Benju; He, Xiju; Li, Shoutian; Xu, Benke; Birnbaumer, Lutz; Liao, Yanhong
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitialdamage and renal fibrosis in obstructed kidneys. Podocyte loss is a characteristic event in diabetic nephropathy(DN). The aim of this study was to examine whether deletion of the closely related diacylglycerol (DAG)-responsiveTRPCs in mice (TRPC3/6/7-/-) affects diabetes-induced renal dysfunction and podocyte loss. We compared urinevolume, kidney hypertrophy, glomerular enlargement, albuminuria and podocyte loss between wild type (WT) andTRPC3/6/7-/- diabetic mice. Finally, we examined whether the TGFβ1 signaling pathway is changed in diabetic WTand TRPC3/6/7-/- mice. TRPC6 protein in the renal cortex was increased in WT diabetic mice. High glucose (HG)treatment increased TRPC6 expression in human podocytes. TRPC3 protein, however, was not altered in eitherdiabetic mice or HG-treated human podocytes. Although diabetic WT and TRPC3/6/7-/- mice had similar levels ofhyperglycemia, the TRPC3/6/7-/- diabetic mice showed less polyuria, kidney hypertrophy, glomerular enlargement,albuminuria, and had lost less podocytes compared with WT diabetic mice. In addition, we observed decreasedexpression of anti-apoptotic Bcl2 and increased expression of pro-apoptotic cleaved caspase 3 in WT diabetic mice,but such changes were not significant in TRPC3/6/7-/- diabetic mice. Western blot and immunohistochemistry revealedthat TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of thesesignaling molecules was not changed in TRPC3/6/7-/- diabetic mice. In conclusion, deletion of DAG-responsiveTRPCs attenuates diabetic renal injury via inhibiting the upregulation of TGFβ1 signaling in diabetic kidneys.
Fil: Liu, Benju. Huazhong University of Science and Technology; China
Fil: He, Xiju. Huazhong University of Science and Technology; China
Fil: Li, Shoutian. Yangtze University; China
Fil: Xu, Benke. Yangtze University; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Liao, Yanhong. Huazhong University of Science and Technology; China
Materia
Deletion of diacylglycerol-responsive
TRPC
diabetic
TGFβ1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/49249
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/49249
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathwayLiu, BenjuHe, XijuLi, ShoutianXu, BenkeBirnbaumer, LutzLiao, YanhongDeletion of diacylglycerol-responsiveTRPCdiabeticTGFβ1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitialdamage and renal fibrosis in obstructed kidneys. Podocyte loss is a characteristic event in diabetic nephropathy(DN). The aim of this study was to examine whether deletion of the closely related diacylglycerol (DAG)-responsiveTRPCs in mice (TRPC3/6/7-/-) affects diabetes-induced renal dysfunction and podocyte loss. We compared urinevolume, kidney hypertrophy, glomerular enlargement, albuminuria and podocyte loss between wild type (WT) andTRPC3/6/7-/- diabetic mice. Finally, we examined whether the TGFβ1 signaling pathway is changed in diabetic WTand TRPC3/6/7-/- mice. TRPC6 protein in the renal cortex was increased in WT diabetic mice. High glucose (HG)treatment increased TRPC6 expression in human podocytes. TRPC3 protein, however, was not altered in eitherdiabetic mice or HG-treated human podocytes. Although diabetic WT and TRPC3/6/7-/- mice had similar levels ofhyperglycemia, the TRPC3/6/7-/- diabetic mice showed less polyuria, kidney hypertrophy, glomerular enlargement,albuminuria, and had lost less podocytes compared with WT diabetic mice. In addition, we observed decreasedexpression of anti-apoptotic Bcl2 and increased expression of pro-apoptotic cleaved caspase 3 in WT diabetic mice,but such changes were not significant in TRPC3/6/7-/- diabetic mice. Western blot and immunohistochemistry revealedthat TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of thesesignaling molecules was not changed in TRPC3/6/7-/- diabetic mice. In conclusion, deletion of DAG-responsiveTRPCs attenuates diabetic renal injury via inhibiting the upregulation of TGFβ1 signaling in diabetic kidneys.Fil: Liu, Benju. Huazhong University of Science and Technology; ChinaFil: He, Xiju. Huazhong University of Science and Technology; ChinaFil: Li, Shoutian. Yangtze University; ChinaFil: Xu, Benke. Yangtze University; ChinaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Liao, Yanhong. Huazhong University of Science and Technology; Chinae Century Publishing2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49249Liu, Benju; He, Xiju; Li, Shoutian; Xu, Benke; Birnbaumer, Lutz; et al.; Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway; e Century Publishing; American Journal of Translational Research; 9; 12; 12-2017; 5619-56301943-8141CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752912/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:12:21Zoai:ri.conicet.gov.ar:11336/49249instacron: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:34982025-10-15 15:12:21.502CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
title Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
spellingShingle Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
Liu, Benju
Deletion of diacylglycerol-responsive
TRPC
diabetic
TGFβ1
title_short Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
title_full Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
title_fullStr Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
title_full_unstemmed Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
title_sort Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
dc.creator.none.fl_str_mv Liu, Benju
He, Xiju
Li, Shoutian
Xu, Benke
Birnbaumer, Lutz
Liao, Yanhong
author Liu, Benju
author_facet Liu, Benju
He, Xiju
Li, Shoutian
Xu, Benke
Birnbaumer, Lutz
Liao, Yanhong
author_role author
author2 He, Xiju
Li, Shoutian
Xu, Benke
Birnbaumer, Lutz
Liao, Yanhong
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Deletion of diacylglycerol-responsive
TRPC
diabetic
TGFβ1
topic Deletion of diacylglycerol-responsive
TRPC
diabetic
TGFβ1
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitialdamage and renal fibrosis in obstructed kidneys. Podocyte loss is a characteristic event in diabetic nephropathy(DN). The aim of this study was to examine whether deletion of the closely related diacylglycerol (DAG)-responsiveTRPCs in mice (TRPC3/6/7-/-) affects diabetes-induced renal dysfunction and podocyte loss. We compared urinevolume, kidney hypertrophy, glomerular enlargement, albuminuria and podocyte loss between wild type (WT) andTRPC3/6/7-/- diabetic mice. Finally, we examined whether the TGFβ1 signaling pathway is changed in diabetic WTand TRPC3/6/7-/- mice. TRPC6 protein in the renal cortex was increased in WT diabetic mice. High glucose (HG)treatment increased TRPC6 expression in human podocytes. TRPC3 protein, however, was not altered in eitherdiabetic mice or HG-treated human podocytes. Although diabetic WT and TRPC3/6/7-/- mice had similar levels ofhyperglycemia, the TRPC3/6/7-/- diabetic mice showed less polyuria, kidney hypertrophy, glomerular enlargement,albuminuria, and had lost less podocytes compared with WT diabetic mice. In addition, we observed decreasedexpression of anti-apoptotic Bcl2 and increased expression of pro-apoptotic cleaved caspase 3 in WT diabetic mice,but such changes were not significant in TRPC3/6/7-/- diabetic mice. Western blot and immunohistochemistry revealedthat TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of thesesignaling molecules was not changed in TRPC3/6/7-/- diabetic mice. In conclusion, deletion of DAG-responsiveTRPCs attenuates diabetic renal injury via inhibiting the upregulation of TGFβ1 signaling in diabetic kidneys.
Fil: Liu, Benju. Huazhong University of Science and Technology; China
Fil: He, Xiju. Huazhong University of Science and Technology; China
Fil: Li, Shoutian. Yangtze University; China
Fil: Xu, Benke. Yangtze University; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Liao, Yanhong. Huazhong University of Science and Technology; China
description TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitialdamage and renal fibrosis in obstructed kidneys. Podocyte loss is a characteristic event in diabetic nephropathy(DN). The aim of this study was to examine whether deletion of the closely related diacylglycerol (DAG)-responsiveTRPCs in mice (TRPC3/6/7-/-) affects diabetes-induced renal dysfunction and podocyte loss. We compared urinevolume, kidney hypertrophy, glomerular enlargement, albuminuria and podocyte loss between wild type (WT) andTRPC3/6/7-/- diabetic mice. Finally, we examined whether the TGFβ1 signaling pathway is changed in diabetic WTand TRPC3/6/7-/- mice. TRPC6 protein in the renal cortex was increased in WT diabetic mice. High glucose (HG)treatment increased TRPC6 expression in human podocytes. TRPC3 protein, however, was not altered in eitherdiabetic mice or HG-treated human podocytes. Although diabetic WT and TRPC3/6/7-/- mice had similar levels ofhyperglycemia, the TRPC3/6/7-/- diabetic mice showed less polyuria, kidney hypertrophy, glomerular enlargement,albuminuria, and had lost less podocytes compared with WT diabetic mice. In addition, we observed decreasedexpression of anti-apoptotic Bcl2 and increased expression of pro-apoptotic cleaved caspase 3 in WT diabetic mice,but such changes were not significant in TRPC3/6/7-/- diabetic mice. Western blot and immunohistochemistry revealedthat TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of thesesignaling molecules was not changed in TRPC3/6/7-/- diabetic mice. In conclusion, deletion of DAG-responsiveTRPCs attenuates diabetic renal injury via inhibiting the upregulation of TGFβ1 signaling in diabetic kidneys.
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/11336/49249
Liu, Benju; He, Xiju; Li, Shoutian; Xu, Benke; Birnbaumer, Lutz; et al.; Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway; e Century Publishing; American Journal of Translational Research; 9; 12; 12-2017; 5619-5630
1943-8141
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49249
identifier_str_mv Liu, Benju; He, Xiju; Li, Shoutian; Xu, Benke; Birnbaumer, Lutz; et al.; Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway; e Century Publishing; American Journal of Translational Research; 9; 12; 12-2017; 5619-5630
1943-8141
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.ncbi.nlm.nih.gov/pmc/articles/PMC5752912/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv e Century Publishing
publisher.none.fl_str_mv e Century Publishing
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 13.22299

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