Analysis of Combined Transcriptomes Identifies Gene Modules that Differentially Respond to Pathogenic Stimulation of Vascular Smooth Muscle and Endothelial Cells.
Sci Rep
; 8(1): 395, 2018 01 10.
Article
em En
| MEDLINE
| ID: mdl-29321689
ABSTRACT
Smooth muscle cells (SMCs) and endothelial cells (ECs) are vital cell types composing the vascular medial wall and the atheroprotective inner lining, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but compromise EC integrity, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMC versus EC) disease-associated regulations remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus-EC differential transcriptomic dynamics, following treatment of human primary SMCs and ECs with TNFα or IL-1ß, both established inducers of SMC hyperplasia and EC dysfunction. As revealed by combined SMC/EC transcriptomes, after TNFα or IL-1ß induction, 174 and 213 genes respectively showed greater up-regulation in SMCs than in ECs (SMC-enriched), while 117 and 138 genes showed greater up-regulation in ECs over SMCs (EC-enriched). Analysis of gene interaction networks identified central genes shared in the two SMC-enriched gene sets, and a distinct group of central genes common in the two EC-enriched gene sets. Significantly, four gene modules (subnetworks) were identified from these central genes, including SMC-enriched JUN and FYN modules and EC-enriched SMAD3 and XPO1 modules. These modules may inform potential intervention targets for selective blockage of SMC hyperplasia without endothelial damage.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
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Citocinas
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Análise de Sequência de RNA
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Perfilação da Expressão Gênica
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Redes Reguladoras de Genes
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article