Journal
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Volume 12, Issue -, Pages 705-715Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/COPD.S128031
Keywords
smoking; COPD; microRNA-149-3p; Toll-like receptor 4; nuclear factor kappa B
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Funding
- National Natural Science Foundation of China [81402991]
- Yunnan Provincial Science and Technology Department [20141A033]
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Background: Smoking is the leading cause of COPD. Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease. This study aims to identify specific circulating microRNAs (miRNAs) from the blood of COPD patients with a long history of smoking. Methods: Blood samples from four different groups were collected, and miRNA microarray was performed. Differential expression of miRNAs was verified by quantitative polymerase chain reaction. In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE) or transfected with miR-149-3p inhibitor/mimics. Protein levels of Toll-like receptor 4 (TLR-4) and nuclear factor kappa B (NF-kappa B) were detected using Western blot and immunofluorescence. Interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha levels were determined by an enzyme-linked immunosorbent assay. Results: miRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups. Expression of miR-149-3p in group C (non-smoker non-COPD) was higher than in group S (smoker non-COPD), S-COPD (smoker with stable COPD) and AE-COPD (smoker with acute exacerbation COPD). CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-kappa B levels in THP-1 cells. Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes. Furthermore, overexpression of miR-149-3p inhibited the TLR-4/NF-kappa B signaling pathways and reduced the secretion of IL-1 beta and TNF-alpha. Conclusion: This study found that smoking can induce differential expression of circulating miRNAs, such as down-regulation of miR-149-3p. Reducing miR-149-3p may increase the inflammatory response in COPD patients through the regulation of the TLR-4/NF-kappa B signaling pathway.
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