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Title: Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype
Author: Coll-Bonfill, Núria
Peinado, 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
Keywords: Artèries
Diferenciació cel·lular
Cicle cel·lular
Factors de transcripció
Múscul llis
Divisió cel·lular
Rates (Animals de laboratori)
Expressió gènica
Cell diferentiation
Cell cycle
Transcription factors
Smooth muscle
Cell division
Rats as laboratory animals
Gene expression
Issue Date: 21-Jul-2016
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2016, vol. 11, num. 7, p. e0159460
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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