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: | , , , , , , |
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Formato: | Artículo |
Lenguaje: | Inglés |
Publicado: |
2020
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Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/9419 |
Aporte de: |
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I33-R139123456789-9419 |
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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 |
work_keys_str_mv |
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bdutipo_str |
Repositorios |
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1764820527977857026 |