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http://hdl.handle.net/2445/119962
Title: | Slug is increased in vascular remodeling and induces a smooth muscle cell proliferative phenotype |
Author: | 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 |
Keywords: | 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 |
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: https://doi.org/10.1371/journal.pone.0159460 |
It is part of: | PLoS One, 2016, vol. 11, num. 7, p. e0159460 |
URI: | http://hdl.handle.net/2445/119962 |
Related resource: | https://doi.org/10.1371/journal.pone.0159460 |
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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