Artículo
MicroRNA dysregulation in pulmonary arteries from chronic obstructive pulmonary disease: Relationships with vascular remodeling
Musri, Melina Mara
; Coll Bonfill, Núria; Maron, Bradley A.; Peinado, Victor Ivo; Wang, Rui Sheng; Altirriba, Jordi; Blanco, Isabel; Oldham, William M.; Tura Ceide, Olga; García Lucio, Jessica; de la Cruz Thea, Benjamín Isaías
; Meister, Gunter; Loscalzo, Joseph; Barberà, Joan A.
Fecha de publicación:
10/2018
Editorial:
American Thoracic Society
Revista:
American Journal Of Respiratory Cell And Molecular Biology
ISSN:
1044-1549
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Pulmonary vascular remodeling is an angiogenic-related process involving changes in smooth muscle cell (SMC) homeostasis, which is frequently observed in chronic obstructive pulmonary disease (COPD). MicroRNAs (miRNAs) are small, noncoding RNAs that regulate mRNA expression levels of many genes, leading to the manifestation of cell identity and specific cellular phenotypes. Here, we evaluate the miRNA expression profiles of pulmonary arteries (PAs) of patients with COPD and its relationship with the regulation of SMC phenotypic change. miRNA expression profiles from PAs of 12 patients with COPD, 9 smokers with normal lung function (SK), and 7 nonsmokers (NS) were analyzed using TaqMan Low-Density Arrays. In patients with COPD, expression levels of miR-98, miR- 139-5p, miR-146b-5p, and miR-451 were upregulated, as compared with NS. In contrast, miR-197, miR-204, miR-485-3p, and miR-627 were downregulated. miRNA-197 expression correlated with both airflowobstruction andPAintimal enlargement. In an in vitro model of SMC differentiation, miR-197 expression was associated with an SMC contractile phenotype. miR-197 inhibition blocked the acquisition of contractile markers in SMCs and promoted a proliferative/migratory phenotypemeasured by both cell cycle analysis and wound-healing assay. Using luciferase assays, Western blot, and quantitative PCR, we confirmed that miR-197 targets the transcription factor E2F1. In PAs from patients with COPD, levels of E2F1 were increased as compared withNS. InPAs of patients with COPD, remodeling of the vesselwall is associated with downregulation of miR-197, which regulates SMC phenotype. The effect ofmiR-197 onPAsmight bemediated, at least in part, by the key proproliferative factor, E2F1.
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Identificadores
Colecciones
Articulos(INIMEC - CONICET)
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Citación
Musri, Melina Mara; Coll Bonfill, Núria; Maron, Bradley A.; Peinado, Victor Ivo; Wang, Rui Sheng; et al.; MicroRNA dysregulation in pulmonary arteries from chronic obstructive pulmonary disease: Relationships with vascular remodeling; American Thoracic Society; American Journal Of Respiratory Cell And Molecular Biology; 59; 4; 10-2018; 490-499
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