PM2.5 downregulates miR-194-3p and accelerates apoptosis in cigarette-inflamed bronchial epithelium by targeting death-associated protein kinase 1
Authors Zhou TY, Zhong YJ, Hu Y, Sun C, Wang YX, Wang GF
Received 19 March 2018
Accepted for publication 17 May 2018
Published 1 August 2018 Volume 2018:13 Pages 2339—2349
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Chunxue Bai
Tianyu Zhou, Yijue Zhong, Yan Hu, Chao Sun, Yunxia Wang, Guangfa Wang
Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China
Background: Persistent exposure to cigarette smoke or biomass fuels induces oxidative stress and apoptosis in bronchial epithelium, which is one of the most important pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Fine particulate matter (PM2.5) is an aggravating risk factor of COPD exacerbation. Animal evidence showed PM2.5accelerated lung inflammation and oxidative stress in COPD mice, but the mechanism is still not clear. Recently, we found that miR-194-3p is a novel biomarker of both COPD and PM2.5 exposure, and miR-194 family has been reported to be involved in cell proliferation and apoptosis. Thus, we propose a hypothesis: PM2.5 can accelerate apoptotic response of airway epithelial cells in COPD and miR-194 is a potential involved regulator.
Materials and methods: Human bronchial epithelial cells (HBEpiCs) were treated with normal media, cigarette smoke solution (CSS) and PM2.5-CSS for 24 h. miR-194-3p mimics, inhibitors and scrambled controls were non-transfected or pre-transfected into HBEpiCs for 48 h. MircroRNAs and mRNA expression were quantified by qRT-PCR. Protein expression was analyzed by western blotting. Caspase activities, mitochondrial membrane potential and TUNEL-positive cells were detected to analyze apoptosis. Bioinformatics and luciferase analysis were used to identify the predicted binding site of miR-194-3p and potential targets.
Results: In our study, we found that PM2.5 significantly aggravated apoptosis in cigarette-inflamed HBEpiCs. miR-194-3p was dramatically downregulated in PM2.5-CSS-treated HBEpiCs. Bioinformatics and luciferase experiments reported that death-associated protein kinase 1 (DAPK1), regulating caspase 3 activities in apoptosis, was directly targeted by miR-194-3p. Inhibition of miR-194-3p increased DAPK1 expression and apoptosis in normal HBEpiCs. Importantly, overexpression of miR-194-3p suppressed apoptosis in PM2.5-CSS HBEpiCs.
Conclusion: These results suggested that miR-194-3p was a protective regulator involved in apoptosis pathway and a potential therapeutic target for treatment of bronchial epithelial injury aggravation induced by PM2.5.
Keywords: fine particulate matter, PM2.5, apoptosis, COPD, bronchial epithelial cells, miR-194-3p
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