| Autor: |
Tania Maes, Francisco Avila Cobos, Ken R. Bracke, Guy Brusselle, Jo Vandesompele, Guy Joos, Pieter Mestdagh, Fien Verhamme, Griet Conickx, Lies Lahousse, Bart M. Vanaudenaerde |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
3.3 Mechanisms of Lung Injury and Repair. |
| DOI: |
10.1183/13993003.congress-2016.pa4025 |
| Popis: |
Rationale: Since aberrant expression of microRNAs (miRNAs) has been implicated in disease pathogenesis, we aimed to identify dysregulated miRNAs in lungs of patients with COPD. Methods: We performed miRNA and mRNA profiling on lung tissue of a screening cohort (n=30) encompassing never smokers, smokers without airflow limitation and smokers with COPD. Differential expression of microRNA-218-5p (miR-218-5p) was validated by RT-qPCR in an independent cohort (n=71). Localization of miR-218-5p was assessed by in situ hybridization. Perturbation of miR-218-5p was obtained by transfecting primary normal human bronchial epithelial (NHBE) cells with a miR-218-5p inhibitor or mimic, followed by polyA-sequencing and RT-qPCR for target genes and markers of inflammation. Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD, compared to never smokers. Decreased pulmonary expression of miR-218-5p was confirmed in an independent validation cohort. Importantly, expression of miR-218-5p strongly correlated with airflow limitation (FEV 1 , FEV 1 /FVC) and lung diffusion (DLCO, KCO). Cellular localization of miR-218-5p revealed highest expression of miR-218-5p in bronchial airway epithelium. Additionally, in vitro perturbation of miR-218-5p in NHBE cells together with gene set enrichment analysis suggest an involvement of miR-218-5p in inflammatory and immune responses. Conclusions: These translational research findings highlight a potential role for miR-218-5p in the pathogenesis of COPD. This abstract has been presented previously at the European Respiratory Society9s Lung Science Conference in March 2016. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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