Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.

Autores
Youakim, Saliba; Karam, Ralph; Smayra, Viviane; Aftimos, Georges; Abramowitz, Joel; Birnbaumer, Lutz; Farès, Nassi
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Transient receptor potential canonical (TRPC) Ca2+-permeant channels, especially TRPC3, are increasinglyimplicated in cardiorenal diseases. We studied the possible role offibroblast TRPC3 in the development ofrenalfibrosis.In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolatedcultured rat renalfibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-sn-glycerol–induced Ca2+entry in thesecells, which was detected by fura-2 Ca2+imaging. TRPC3 blockade or Ca2+removal inhibitedfibroblastproliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibitedfibrosis and inflammation-associated markers in anoncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologicfind-ings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 ex-pression increased in thefibroblasts of obstructed kidneys and was associated with increased Ca2+entry,ERK1/2 phosphorylation, andfibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout inmice inhibited ERK1/2 phosphorylation andfibroblast activation as well as myofibroblast differentiationand extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damageand renalfibrosis. In conclusion, TRPC3 channels are present in renalfibroblasts and controlfibroblastproliferation, differentiation, and activation through Ca2+-mediated ERK signaling. TRPC3 channels mightconstitute important therapeutic targets for improving renal remodeling in kidney disease.
Fil: Youakim, Saliba. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; Líbano
Fil: Karam, Ralph. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; Líbano
Fil: Smayra, Viviane. Saint Joseph University. Faculty of Medicine; Líbano
Fil: Aftimos, Georges. National Instituteof Pathology. Department of Anatomopathology; Líbano
Fil: Abramowitz, Joel. National Institute of Environmental Health Sciences. Laboratory of Neurobiology ; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology ; Estados Unidos
Fil: Farès, Nassi. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; Líbano
Materia
FIBROBLAST
RENAL FIBROSIS
ION CHANNEL
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:11336/98748
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98748
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.Youakim, SalibaKaram, RalphSmayra, VivianeAftimos, GeorgesAbramowitz, JoelBirnbaumer, LutzFarès, NassiFIBROBLASTRENAL FIBROSISION CHANNELhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Transient receptor potential canonical (TRPC) Ca2+-permeant channels, especially TRPC3, are increasinglyimplicated in cardiorenal diseases. We studied the possible role offibroblast TRPC3 in the development ofrenalfibrosis.In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolatedcultured rat renalfibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-sn-glycerol–induced Ca2+entry in thesecells, which was detected by fura-2 Ca2+imaging. TRPC3 blockade or Ca2+removal inhibitedfibroblastproliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibitedfibrosis and inflammation-associated markers in anoncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologicfind-ings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 ex-pression increased in thefibroblasts of obstructed kidneys and was associated with increased Ca2+entry,ERK1/2 phosphorylation, andfibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout inmice inhibited ERK1/2 phosphorylation andfibroblast activation as well as myofibroblast differentiationand extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damageand renalfibrosis. In conclusion, TRPC3 channels are present in renalfibroblasts and controlfibroblastproliferation, differentiation, and activation through Ca2+-mediated ERK signaling. TRPC3 channels mightconstitute important therapeutic targets for improving renal remodeling in kidney disease.Fil: Youakim, Saliba. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; LíbanoFil: Karam, Ralph. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; LíbanoFil: Smayra, Viviane. Saint Joseph University. Faculty of Medicine; LíbanoFil: Aftimos, Georges. National Instituteof Pathology. Department of Anatomopathology; LíbanoFil: Abramowitz, Joel. National Institute of Environmental Health Sciences. Laboratory of Neurobiology ; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology ; Estados UnidosFil: Farès, Nassi. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; LíbanoAmerican Society of Nephrology2014-09-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98748Youakim, Saliba; Karam, Ralph; Smayra, Viviane; Aftimos, Georges; Abramowitz, Joel; et al.; Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.; American Society of Nephrology; Journal of the American Society of Nephrology; 26; 8; 23-9-2014; 1855-18761046-66731533-3450CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://jasn.asnjournals.org/content/26/8/1855info:eu-repo/semantics/altIdentifier/doi/10.1681/ASN.2014010065info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:06Zoai:ri.conicet.gov.ar:11336/98748instacron: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 10:09:07.125CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.
title Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.
spellingShingle Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.
Youakim, Saliba
FIBROBLAST
RENAL FIBROSIS
ION CHANNEL
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.
dc.creator.none.fl_str_mv Youakim, Saliba
Karam, Ralph
Smayra, Viviane
Aftimos, Georges
Abramowitz, Joel
Birnbaumer, Lutz
Farès, Nassi
author Youakim, Saliba
author_facet Youakim, Saliba
Karam, Ralph
Smayra, Viviane
Aftimos, Georges
Abramowitz, Joel
Birnbaumer, Lutz
Farès, Nassi
author_role author
author2 Karam, Ralph
Smayra, Viviane
Aftimos, Georges
Abramowitz, Joel
Birnbaumer, Lutz
Farès, Nassi
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FIBROBLAST
RENAL FIBROSIS
ION CHANNEL
topic FIBROBLAST
RENAL FIBROSIS
ION CHANNEL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Transient receptor potential canonical (TRPC) Ca2+-permeant channels, especially TRPC3, are increasinglyimplicated in cardiorenal diseases. We studied the possible role offibroblast TRPC3 in the development ofrenalfibrosis.In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolatedcultured rat renalfibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-sn-glycerol–induced Ca2+entry in thesecells, which was detected by fura-2 Ca2+imaging. TRPC3 blockade or Ca2+removal inhibitedfibroblastproliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibitedfibrosis and inflammation-associated markers in anoncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologicfind-ings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 ex-pression increased in thefibroblasts of obstructed kidneys and was associated with increased Ca2+entry,ERK1/2 phosphorylation, andfibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout inmice inhibited ERK1/2 phosphorylation andfibroblast activation as well as myofibroblast differentiationand extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damageand renalfibrosis. In conclusion, TRPC3 channels are present in renalfibroblasts and controlfibroblastproliferation, differentiation, and activation through Ca2+-mediated ERK signaling. TRPC3 channels mightconstitute important therapeutic targets for improving renal remodeling in kidney disease.
Fil: Youakim, Saliba. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; Líbano
Fil: Karam, Ralph. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; Líbano
Fil: Smayra, Viviane. Saint Joseph University. Faculty of Medicine; Líbano
Fil: Aftimos, Georges. National Instituteof Pathology. Department of Anatomopathology; Líbano
Fil: Abramowitz, Joel. National Institute of Environmental Health Sciences. Laboratory of Neurobiology ; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology ; Estados Unidos
Fil: Farès, Nassi. Faculty of Medicine. Pole of Technology and Health. Physiology and Pathophysiology Research Laboratory; Líbano
description Transient receptor potential canonical (TRPC) Ca2+-permeant channels, especially TRPC3, are increasinglyimplicated in cardiorenal diseases. We studied the possible role offibroblast TRPC3 in the development ofrenalfibrosis.In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolatedcultured rat renalfibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-sn-glycerol–induced Ca2+entry in thesecells, which was detected by fura-2 Ca2+imaging. TRPC3 blockade or Ca2+removal inhibitedfibroblastproliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibitedfibrosis and inflammation-associated markers in anoncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologicfind-ings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 ex-pression increased in thefibroblasts of obstructed kidneys and was associated with increased Ca2+entry,ERK1/2 phosphorylation, andfibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout inmice inhibited ERK1/2 phosphorylation andfibroblast activation as well as myofibroblast differentiationand extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damageand renalfibrosis. In conclusion, TRPC3 channels are present in renalfibroblasts and controlfibroblastproliferation, differentiation, and activation through Ca2+-mediated ERK signaling. TRPC3 channels mightconstitute important therapeutic targets for improving renal remodeling in kidney disease.
publishDate 2014
dc.date.none.fl_str_mv 2014-09-23
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/11336/98748
Youakim, Saliba; Karam, Ralph; Smayra, Viviane; Aftimos, Georges; Abramowitz, Joel; et al.; Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.; American Society of Nephrology; Journal of the American Society of Nephrology; 26; 8; 23-9-2014; 1855-1876
1046-6673
1533-3450
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98748
identifier_str_mv Youakim, Saliba; Karam, Ralph; Smayra, Viviane; Aftimos, Georges; Abramowitz, Joel; et al.; Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis.; American Society of Nephrology; Journal of the American Society of Nephrology; 26; 8; 23-9-2014; 1855-1876
1046-6673
1533-3450
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://jasn.asnjournals.org/content/26/8/1855
info:eu-repo/semantics/altIdentifier/doi/10.1681/ASN.2014010065
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 American Society of Nephrology
publisher.none.fl_str_mv American Society of Nephrology
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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