MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease
| Autor: | Jo Vandesompele, Guy Joos, Guy Brusselle, Yannick M.T.A. van Durme, Olivier Thas, Ken R. Bracke, Pieter Mestdagh, Geert R. Van Pottelberge |
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| Rok vydání: | 2010 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Enzyme-Linked Immunosorbent Assay Critical Care and Intensive Care Medicine Severity of Illness Index Bronchial Provocation Tests Statistics Nonparametric law.invention Cohort Studies Pulmonary Disease Chronic Obstructive law Reference Values microRNA medicine Humans Gene Polymerase chain reaction In Situ Hybridization Asthma Aged Regulation of gene expression COPD Lung business.industry Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Smoking Sputum Middle Aged medicine.disease respiratory tract diseases Respiratory Function Tests MicroRNAs medicine.anatomical_structure Gene Expression Regulation Immunology Linear Models Female medicine.symptom business Biomarkers |
| Zdroj: | American journal of respiratory and critical care medicine. 183(7) |
| ISSN: | 1535-4970 |
| Popis: | Chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation in the airways and lungs combined with disturbed homeostatic functions of pulmonary cells. MicroRNAs (miRNAs) have the ability to regulate these processes by interfering with gene transcription and translation.We aimed to identify miRNA expression in induced sputum and examined whether the expression of miRNAs differed between patients with COPD and subjects without airflow limitation.Expression of 627 miRNAs was evaluated in induced sputum supernatant of 32 subjects by stem-loop reverse transcription-quantitative polymerase chain reaction. Differentially expressed miRNAs were validated in an independent replication cohort of 41 subjects. Enrichment of miRNA target genes was identified by in silico analysis. Protein expression of target genes was determined by ELISA.Thirty-four miRNAs were differentially expressed between never-smokers and current smokers without airflow limitation in the screening cohort. Eight miRNAs were expressed at a significantly lower level in current-smoking patients with COPD compared with never-smokers without airflow limitation. Reduced expression of let-7c and miR-125b in patients with COPD compared with healthy subjects was confirmed in the validation cohort. Target genes of let-7c were significantly enriched in the sputum of patients with severe COPD. The concentration of tumor necrosis factor receptor type II (TNFR-II, implicated in COPD pathogenesis and a predicted target gene of let-7c) was inversely correlated with the sputum levels of let-7c .let-7c is significantly reduced in the sputum of currently smoking patients with COPD and is associated with increased expression of TNFR-II. |
| Databáze: | OpenAIRE |
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