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

Abstract: TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitial damage 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 closel...

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Detalles Bibliográficos
Autores principales: Liu, Benju, He, Xiju, Li, Shoutian, Xu, Benke, Birnbaumer, Lutz, Liao, Yanhong
Formato: Artículo
Lenguaje:Inglés
Publicado: e-Century Publishing 2019
Materias:
GLUCOSA
HIPERGLUCEMIA
ENFERMEDADES RENALES
RIÑON
FIBROSIS
DIABETES
Acceso en línea:http://www.ajtr.org/V9_No12.html
https://repositorio.uca.edu.ar/handle/123456789/8708
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8708
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic GLUCOSA
HIPERGLUCEMIA
ENFERMEDADES RENALES
RIÑON
FIBROSIS
DIABETES
spellingShingle GLUCOSA
HIPERGLUCEMIA
ENFERMEDADES RENALES
RIÑON
FIBROSIS
DIABETES
Liu, Benju
He, Xiju
Li, Shoutian
Xu, Benke
Birnbaumer, Lutz
Liao, Yanhong
Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
topic_facet GLUCOSA
HIPERGLUCEMIA
ENFERMEDADES RENALES
RIÑON
FIBROSIS
DIABETES
description Abstract: TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitial damage 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)-responsive TRPCs in mice (TRPC3/6/7-/-) affects diabetes-induced renal dysfunction and podocyte loss. We compared urine volume, kidney hypertrophy, glomerular enlargement, albuminuria and podocyte loss between wild type (WT) and TRPC3/6/7-/- diabetic mice. Finally, we examined whether the TGFβ1 signaling pathway is changed in diabetic WT and 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 either diabetic mice or HG-treated human podocytes. Although diabetic WT and TRPC3/6/7-/- mice had similar levels of hyperglycemia, 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 decreased expression 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 revealed that TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of these signaling molecules was not changed in TRPC3/6/7-/- diabetic mice. In conclusion, deletion of DAG-responsive TRPCs attenuates diabetic renal injury via inhibiting the upregulation of TGFβ1 signaling in diabetic kidneys.
format Artículo
author Liu, Benju
He, Xiju
Li, Shoutian
Xu, Benke
Birnbaumer, Lutz
Liao, Yanhong
author_facet Liu, Benju
He, Xiju
Li, Shoutian
Xu, Benke
Birnbaumer, Lutz
Liao, Yanhong
author_sort Liu, Benju
title Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway
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
publisher e-Century Publishing
publishDate 2019
url http://www.ajtr.org/V9_No12.html
https://repositorio.uca.edu.ar/handle/123456789/8708
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