已发表论文

微 RNA-149-3p 对 Toll 样受体-4 的抑制与吸烟相关的 COPD 有关

 

Authors Shen W, Liu J, Zhao G, Fan M, Song G, Zhang Y, Weng Z, Zhang Y

Received 17 November 2016

Accepted for publication 27 December 2016

Published 22 February 2017 Volume 2017:12 Pages 705—715

DOI https://doi.org/10.2147/COPD.S128031

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell

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 κB (NF-κB) were detected using Western blot and immunofluorescence. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α 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-κB 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-κB signaling pathways and reduced the secretion of IL-1β and TNF-α.
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-κB signaling pathway.
Keywords: smoking, COPD, microRNA-149-3p, Toll-like receptor 4, nuclear factor κB