Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype

Autores
Coll Bonfill, Núria; Peinado, Victor I.; Pisano, María Victoria; Párrizas, Marcelina; Blanco, Isabel; Evers, Maurits; Engelmann, Julia C.; García Lucio, Jessica; Tura Ceide, Olga; Meister, Gunter; Barberà, Joan Albert; Musri, Melina Mara
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective : Previous studies have confirmed Slug as a key player in regulating phenotypic changes in several cell models, however, its role in smooth muscle cells (SMC) has never been assessed. The purpose of this study was to evaluate the expression of Slug during the phenotypic switch of SMC in vitro and throughout the development of vascular remodeling. Methods and Results : Slug expression was decreased during both cell-to-cell contact and TGFβ1 induced SMC differentiation. Tumor necrosis factor-α (TNFα), a known inductor of a proliferative/dedifferentiated SMC phenotype, induces the expression of Slug in SMC. Slug knockdown blocked TNFα-induced SMC phenotypic change and significantly reduced both SMC proliferation and migration, while its overexpression blocked the TGFβ1-induced SMC differentiation and induced proliferation and migration. Genome-wide transcriptomic analysis showed that in SMC, Slug knockdown induced changes mainly in genes related to proliferation and migration, indicating that Slug controls these processes in SMC. Notably, Slug expression was significantly up-regulated in lungs of mice using a model of pulmonary hypertension-related vascular remodeling. Highly remodeled human pulmonary arteries also showed an increase of Slug expression compared to less remodeled arteries. Conclusions : Slug emerges as a key transcription factor driving SMC towards a proliferative phenotype. The increased Slug expression observed in vivo in highly remodeled arteries of mice and human suggests a role of Slug in the pathogenesis of pulmonary vascular diseases.
Fil: Coll Bonfill, Núria. Universidad de Barcelona; España
Fil: Peinado, Victor I.. Universidad de Barcelona; España. CIBER Enfermedades Respiratorias; España
Fil: Pisano, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Párrizas, Marcelina. CIBER Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Blanco, Isabel. Universidad de Barcelona; España
Fil: Evers, Maurits. Universitat Regensburg; Alemania
Fil: Engelmann, Julia C.. Universitat Regensburg; Alemania
Fil: García Lucio, Jessica. Universidad de Barcelona; España
Fil: Tura Ceide, Olga. CIBER Enfermedades Respiratorias; España
Fil: Meister, Gunter. Universitat Regensburg; Alemania
Fil: Barberà, Joan Albert. Universidad de Barcelona; España
Fil: Musri, Melina Mara. Universidad de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Materia
SMOOTH MUSCLE CELLS
PHENOTYPIC SWITCH
VASCULAR REMODELING
SLUG
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:11336/75176
Acceder
id CONICETDig_03acf9c5d71e2f04f2885ec872c3db2a
oai_identifier_str oai:ri.conicet.gov.ar:11336/75176
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotypeColl Bonfill, NúriaPeinado, Victor I.Pisano, María VictoriaPárrizas, MarcelinaBlanco, IsabelEvers, MauritsEngelmann, Julia C.García Lucio, JessicaTura Ceide, OlgaMeister, GunterBarberà, Joan AlbertMusri, Melina MaraSMOOTH MUSCLE CELLSPHENOTYPIC SWITCHVASCULAR REMODELINGSLUGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective : Previous studies have confirmed Slug as a key player in regulating phenotypic changes in several cell models, however, its role in smooth muscle cells (SMC) has never been assessed. The purpose of this study was to evaluate the expression of Slug during the phenotypic switch of SMC in vitro and throughout the development of vascular remodeling. Methods and Results : Slug expression was decreased during both cell-to-cell contact and TGFβ1 induced SMC differentiation. Tumor necrosis factor-α (TNFα), a known inductor of a proliferative/dedifferentiated SMC phenotype, induces the expression of Slug in SMC. Slug knockdown blocked TNFα-induced SMC phenotypic change and significantly reduced both SMC proliferation and migration, while its overexpression blocked the TGFβ1-induced SMC differentiation and induced proliferation and migration. Genome-wide transcriptomic analysis showed that in SMC, Slug knockdown induced changes mainly in genes related to proliferation and migration, indicating that Slug controls these processes in SMC. Notably, Slug expression was significantly up-regulated in lungs of mice using a model of pulmonary hypertension-related vascular remodeling. Highly remodeled human pulmonary arteries also showed an increase of Slug expression compared to less remodeled arteries. Conclusions : Slug emerges as a key transcription factor driving SMC towards a proliferative phenotype. The increased Slug expression observed in vivo in highly remodeled arteries of mice and human suggests a role of Slug in the pathogenesis of pulmonary vascular diseases.Fil: Coll Bonfill, Núria. Universidad de Barcelona; EspañaFil: Peinado, Victor I.. Universidad de Barcelona; España. CIBER Enfermedades Respiratorias; EspañaFil: Pisano, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Párrizas, Marcelina. CIBER Diabetes y Enfermedades Metabólicas Asociadas; EspañaFil: Blanco, Isabel. Universidad de Barcelona; EspañaFil: Evers, Maurits. Universitat Regensburg; AlemaniaFil: Engelmann, Julia C.. Universitat Regensburg; AlemaniaFil: García Lucio, Jessica. Universidad de Barcelona; EspañaFil: Tura Ceide, Olga. CIBER Enfermedades Respiratorias; EspañaFil: Meister, Gunter. Universitat Regensburg; AlemaniaFil: Barberà, Joan Albert. Universidad de Barcelona; EspañaFil: Musri, Melina Mara. Universidad de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaPublic Library of Science2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/75176Coll Bonfill, Núria; Peinado, Victor I.; Pisano, María Victoria; Párrizas, Marcelina; Blanco, Isabel; et al.; Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype; Public Library of Science; Plos One; 11; 7; 7-2016; 1-21; e01594601932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0159460info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159460info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:00Zoai:ri.conicet.gov.ar:11336/75176instacron: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 10:08:00.876CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
title Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
spellingShingle Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
Coll Bonfill, Núria
SMOOTH MUSCLE CELLS
PHENOTYPIC SWITCH
VASCULAR REMODELING
SLUG
title_short Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
title_full Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
title_fullStr Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
title_full_unstemmed Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
title_sort Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
dc.creator.none.fl_str_mv Coll Bonfill, Núria
Peinado, Victor I.
Pisano, María Victoria
Párrizas, Marcelina
Blanco, Isabel
Evers, Maurits
Engelmann, Julia C.
García Lucio, Jessica
Tura Ceide, Olga
Meister, Gunter
Barberà, Joan Albert
Musri, Melina Mara
author Coll Bonfill, Núria
author_facet Coll Bonfill, Núria
Peinado, Victor I.
Pisano, María Victoria
Párrizas, Marcelina
Blanco, Isabel
Evers, Maurits
Engelmann, Julia C.
García Lucio, Jessica
Tura Ceide, Olga
Meister, Gunter
Barberà, Joan Albert
Musri, Melina Mara
author_role author
author2 Peinado, Victor I.
Pisano, María Victoria
Párrizas, Marcelina
Blanco, Isabel
Evers, Maurits
Engelmann, Julia C.
García Lucio, Jessica
Tura Ceide, Olga
Meister, Gunter
Barberà, Joan Albert
Musri, Melina Mara
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SMOOTH MUSCLE CELLS
PHENOTYPIC SWITCH
VASCULAR REMODELING
SLUG
topic SMOOTH MUSCLE CELLS
PHENOTYPIC SWITCH
VASCULAR REMODELING
SLUG
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective : Previous studies have confirmed Slug as a key player in regulating phenotypic changes in several cell models, however, its role in smooth muscle cells (SMC) has never been assessed. The purpose of this study was to evaluate the expression of Slug during the phenotypic switch of SMC in vitro and throughout the development of vascular remodeling. Methods and Results : Slug expression was decreased during both cell-to-cell contact and TGFβ1 induced SMC differentiation. Tumor necrosis factor-α (TNFα), a known inductor of a proliferative/dedifferentiated SMC phenotype, induces the expression of Slug in SMC. Slug knockdown blocked TNFα-induced SMC phenotypic change and significantly reduced both SMC proliferation and migration, while its overexpression blocked the TGFβ1-induced SMC differentiation and induced proliferation and migration. Genome-wide transcriptomic analysis showed that in SMC, Slug knockdown induced changes mainly in genes related to proliferation and migration, indicating that Slug controls these processes in SMC. Notably, Slug expression was significantly up-regulated in lungs of mice using a model of pulmonary hypertension-related vascular remodeling. Highly remodeled human pulmonary arteries also showed an increase of Slug expression compared to less remodeled arteries. Conclusions : Slug emerges as a key transcription factor driving SMC towards a proliferative phenotype. The increased Slug expression observed in vivo in highly remodeled arteries of mice and human suggests a role of Slug in the pathogenesis of pulmonary vascular diseases.
Fil: Coll Bonfill, Núria. Universidad de Barcelona; España
Fil: Peinado, Victor I.. Universidad de Barcelona; España. CIBER Enfermedades Respiratorias; España
Fil: Pisano, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Párrizas, Marcelina. CIBER Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Blanco, Isabel. Universidad de Barcelona; España
Fil: Evers, Maurits. Universitat Regensburg; Alemania
Fil: Engelmann, Julia C.. Universitat Regensburg; Alemania
Fil: García Lucio, Jessica. Universidad de Barcelona; España
Fil: Tura Ceide, Olga. CIBER Enfermedades Respiratorias; España
Fil: Meister, Gunter. Universitat Regensburg; Alemania
Fil: Barberà, Joan Albert. Universidad de Barcelona; España
Fil: Musri, Melina Mara. Universidad de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
description Objective : Previous studies have confirmed Slug as a key player in regulating phenotypic changes in several cell models, however, its role in smooth muscle cells (SMC) has never been assessed. The purpose of this study was to evaluate the expression of Slug during the phenotypic switch of SMC in vitro and throughout the development of vascular remodeling. Methods and Results : Slug expression was decreased during both cell-to-cell contact and TGFβ1 induced SMC differentiation. Tumor necrosis factor-α (TNFα), a known inductor of a proliferative/dedifferentiated SMC phenotype, induces the expression of Slug in SMC. Slug knockdown blocked TNFα-induced SMC phenotypic change and significantly reduced both SMC proliferation and migration, while its overexpression blocked the TGFβ1-induced SMC differentiation and induced proliferation and migration. Genome-wide transcriptomic analysis showed that in SMC, Slug knockdown induced changes mainly in genes related to proliferation and migration, indicating that Slug controls these processes in SMC. Notably, Slug expression was significantly up-regulated in lungs of mice using a model of pulmonary hypertension-related vascular remodeling. Highly remodeled human pulmonary arteries also showed an increase of Slug expression compared to less remodeled arteries. Conclusions : Slug emerges as a key transcription factor driving SMC towards a proliferative phenotype. The increased Slug expression observed in vivo in highly remodeled arteries of mice and human suggests a role of Slug in the pathogenesis of pulmonary vascular diseases.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
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/11336/75176
Coll Bonfill, Núria; Peinado, Victor I.; Pisano, María Victoria; Párrizas, Marcelina; Blanco, Isabel; et al.; Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype; Public Library of Science; Plos One; 11; 7; 7-2016; 1-21; e0159460
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/75176
identifier_str_mv Coll Bonfill, Núria; Peinado, Victor I.; Pisano, María Victoria; Párrizas, Marcelina; Blanco, Isabel; et al.; Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype; Public Library of Science; Plos One; 11; 7; 7-2016; 1-21; e0159460
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0159460
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159460
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
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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