Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis

Abstract: Transient receptor potential canonical (TRPC) Ca -permeant channels, especially TRPC3, are increasingly implicated in cardiorenal diseases. We studied the possible role of fibroblast TRPC3 in the development of renal fibrosis. In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6...

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Autores principales: Saliba, Youakim, Karam, Ralph, Smayra, Viviane, Aftimos, Georges, Abramowitz, Joel, Birnbaumer, Lutz, Farès, Nassim
Formato: Artículo
Lenguaje:Inglés
Publicado: 2020
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Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9419
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id I33-R139123456789-9419
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 ENFERMEDADES RENALES
ENFERMEDADES CARDIOVASCULARES
FIBROSIS
CALCIO
CANALES IONICOS
spellingShingle ENFERMEDADES RENALES
ENFERMEDADES CARDIOVASCULARES
FIBROSIS
CALCIO
CANALES IONICOS
Saliba, Youakim
Karam, Ralph
Smayra, Viviane
Aftimos, Georges
Abramowitz, Joel
Birnbaumer, Lutz
Farès, Nassim
Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis
topic_facet ENFERMEDADES RENALES
ENFERMEDADES CARDIOVASCULARES
FIBROSIS
CALCIO
CANALES IONICOS
description Abstract: Transient receptor potential canonical (TRPC) Ca -permeant channels, especially TRPC3, are increasingly implicated in cardiorenal diseases. We studied the possible role of fibroblast TRPC3 in the development of renal fibrosis. In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolated cultured rat renal fibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3 was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-snglycerol– induced Ca entry in these cells, which was detected by fura-2 Ca imaging. TRPC3 blockade or Ca removal inhibited fibroblast proliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibited fibrosis and inflammation-associated markers in a noncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologic findings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 expression increased in the fibroblasts of obstructed kidneys and was associated with increased Ca entry, ERK1/2 phosphorylation, and fibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout in mice inhibited ERK1/2 phosphorylation and fibroblast activation as well as myofibroblast differentiation and extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damage and renal fibrosis. In conclusion, TRPC3 channels are present in renal fibroblasts and control fibroblast proliferation, differentiation, and activation through Ca -mediated ERK signaling. TRPC3 channels might constitute important therapeutic targets for improving renal remodeling in kidney disease.
format Artículo
author Saliba, Youakim
Karam, Ralph
Smayra, Viviane
Aftimos, Georges
Abramowitz, Joel
Birnbaumer, Lutz
Farès, Nassim
author_facet Saliba, Youakim
Karam, Ralph
Smayra, Viviane
Aftimos, Georges
Abramowitz, Joel
Birnbaumer, Lutz
Farès, Nassim
author_sort Saliba, Youakim
title Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis
title_short Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis
title_full Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis
title_fullStr Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis
title_full_unstemmed Evidence of a role for fibroblast transient receptor potential canonical 3 Ca2+ channel in renal fibrosis
title_sort evidence of a role for fibroblast transient receptor potential canonical 3 ca2+ channel in renal fibrosis
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9419
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