Slug is Increased in Vascular Remodeling and Induces a Smooth Muscle Cell Proliferative Phenotype
| Autor: | Julia C. Engelmann, Jéssica García-Lucio, María V. Pisano, Olga Tura-Ceide, Núria Coll-Bonfill, Joan Albert Barberà, Melina M. Musri, Isabel Blanco, Gunter Meister, Marcelina Párrizas, Maurits Evers, Victor I. Peinado |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2016 |
| Předmět: |
Cellular differentiation
Cell Artificial Gene Amplification and Extension Cicle cel·lular Biochemistry Polymerase Chain Reaction 0302 clinical medicine Cell Movement 570 Biowissenschaften Biologie Cell Cycle and Cell Division lcsh:Science Lung Regulation of gene expression Gene knockdown purl.org/becyt/ford/3.1 [https] Arteries Cell biology Medicina Básica Phenotypes 030220 oncology & carcinogenesis cardiovascular system purl.org/becyt/ford/3 [https] Diferenciació cel·lular Slug Hypertension Pulmonary TUMOR-NECROSIS-FACTOR EPITHELIAL-MESENCHYMAL TRANSITION OBSTRUCTIVE PULMONARY-DISEASE BREAST-CANCER CELLS TRANSCRIPTION FACTOR GENE-EXPRESSION GROWTH-FACTOR PROGENITOR CELLS MILD COPD MODULATION Vascular Remodeling Cell cycle 03 medical and health sciences DNA-binding proteins Genetics Transcription factors Humans Molecular Biology Techniques Molecular Biology Artèries Tumor Necrosis Factor-alpha lcsh:R fungi Proteins Correction Reverse Transcriptase-Polymerase Chain Reaction Regulatory Proteins Mice Inbred C57BL 030104 developmental biology Divisió cel·lular Factors de transcripció Blood Vessels lcsh:Q Gene expression Developmental Biology Transcription Factors 0301 basic medicine 610 Medizin lcsh:Medicine Gene Expression SLUG Medicine and Health Sciences Myocyte Pulmonary Arteries Rates (Animals de laboratori) ddc:610 Multidisciplinary Otras Medicina Básica Cell Differentiation Múscul llis Animal Models musculoskeletal system Phenotype PHENOTYPIC SWITCH medicine.anatomical_structure Cell Processes embryonic structures Female ddc:570 Anatomy Research Article CIENCIAS MÉDICAS Y DE LA SALUD animal structures Cell division Myocytes Smooth Muscle Rats as laboratory animals Mouse Models Biology Pulmonary Artery Research and Analysis Methods Models Biological Transforming Growth Factor beta1 Model Organisms Smooth muscle Cell diferentiation medicine Animals Gene Regulation SMOOTH MUSCLE CELLS Cell Proliferation Biology and life sciences Cell growth Cell Biology Cell Dedifferentiation biology.organism_classification Expressió gènica Disease Models Animal VASCULAR REMODELING Gene Expression Regulation Cardiovascular Anatomy Snail Family Transcription Factors |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona PLoS ONE CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Recercat. Dipósit de la Recerca de Catalunya instname PLoS ONE, Vol 11, Iss 7, p e0159460 (2016) |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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