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

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 vitr...

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Autores: Coll-Bonfill, Núria, Peinado Cabré, Víctor Ivo, Pisano, Maria V., Párrizas, Marcelina, Blanco Vich, Isabel, Evers, Maurits, Engelmann, Julia C., García-Lucio, Jéssica, Tura-Ceide, Olga, Meister, Gunter, Barberà i Mir, Joan Albert, Musri, Melina Mara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/119962
Acceso en línea:https://hdl.handle.net/2445/119962
Access Level:acceso abierto
Palabra clave:Artèries
Diferenciació cel·lular
Cicle cel·lular
Factors de transcripció
Múscul llis
Divisió cel·lular
Rates (Animals de laboratori)
Expressió gènica
Arteries
Cell diferentiation
Cell cycle
Transcription factors
Smooth muscle
Cell division
Rats as laboratory animals
Gene expression
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spelling Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotypeColl-Bonfill, NúriaPeinado Cabré, Víctor IvoPisano, Maria V.Párrizas, MarcelinaBlanco Vich, IsabelEvers, MauritsEngelmann, Julia C.García-Lucio, JéssicaTura-Ceide, OlgaMeister, GunterBarberà i Mir, Joan AlbertMusri, Melina MaraArtèriesDiferenciació cel·lularCicle cel·lularFactors de transcripcióMúscul llisDivisió cel·lularRates (Animals de laboratori)Expressió gènicaArteriesCell diferentiationCell cycleTranscription factorsSmooth muscleCell divisionRats as laboratory animalsGene expressionObjective 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.Public Library of Science (PLoS)2018201820162018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion21 p.application/pdfhttps://hdl.handle.net/2445/119962Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0159460PLoS One, 2016, vol. 11, num. 7, p. e0159460https://doi.org/10.1371/journal.pone.0159460cc-by (c) Coll-Bonfill, Núria et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1199622026-05-29T05:05:01Z
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
Artèries
Diferenciació cel·lular
Cicle cel·lular
Factors de transcripció
Múscul llis
Divisió cel·lular
Rates (Animals de laboratori)
Expressió gènica
Arteries
Cell diferentiation
Cell cycle
Transcription factors
Smooth muscle
Cell division
Rats as laboratory animals
Gene expression
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 Cabré, Víctor Ivo
Pisano, Maria V.
Párrizas, Marcelina
Blanco Vich, Isabel
Evers, Maurits
Engelmann, Julia C.
García-Lucio, Jéssica
Tura-Ceide, Olga
Meister, Gunter
Barberà i Mir, Joan Albert
Musri, Melina Mara
author Coll-Bonfill, Núria
author_facet Coll-Bonfill, Núria
Peinado Cabré, Víctor Ivo
Pisano, Maria V.
Párrizas, Marcelina
Blanco Vich, Isabel
Evers, Maurits
Engelmann, Julia C.
García-Lucio, Jéssica
Tura-Ceide, Olga
Meister, Gunter
Barberà i Mir, Joan Albert
Musri, Melina Mara
author_role author
author2 Peinado Cabré, Víctor Ivo
Pisano, Maria V.
Párrizas, Marcelina
Blanco Vich, Isabel
Evers, Maurits
Engelmann, Julia C.
García-Lucio, Jéssica
Tura-Ceide, Olga
Meister, Gunter
Barberà i Mir, Joan Albert
Musri, Melina Mara
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Artèries
Diferenciació cel·lular
Cicle cel·lular
Factors de transcripció
Múscul llis
Divisió cel·lular
Rates (Animals de laboratori)
Expressió gènica
Arteries
Cell diferentiation
Cell cycle
Transcription factors
Smooth muscle
Cell division
Rats as laboratory animals
Gene expression
topic Artèries
Diferenciació cel·lular
Cicle cel·lular
Factors de transcripció
Múscul llis
Divisió cel·lular
Rates (Animals de laboratori)
Expressió gènica
Arteries
Cell diferentiation
Cell cycle
Transcription factors
Smooth muscle
Cell division
Rats as laboratory animals
Gene expression
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
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/119962
url https://hdl.handle.net/2445/119962
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0159460
PLoS One, 2016, vol. 11, num. 7, p. e0159460
https://doi.org/10.1371/journal.pone.0159460
dc.rights.none.fl_str_mv cc-by (c) Coll-Bonfill, Núria et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Coll-Bonfill, Núria et al., 2016
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 21 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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