论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
Authors He X, Li T, Kang N, Zeng H, Ren S, Zong D, Li J, Cai S, Chen P, Chen Y
Received 26 June 2017
Accepted for publication 26 September 2017
Published 3 November 2017 Volume 2017:12 Pages 3245—3254
DOI https://doi.org/10.2147/COPD.S144881
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: Cigarette smoke exposure is the most common risk factor for emphysema,
which is one of the major pathologies of COPD. Protein arginine
methyltransferase 6 (PRMT6) is a nuclear enzyme that specially catalyzes
dimethylation of R2 in histone H3 (H3R2me2a). H3R2me2a prevents trimethylation
of H3K4 (H3K4me3), which is located in the transcription start sites of genes
in mammalian genomes. We attempted to determine the expression of PRMT6 in
human samples, and investigate whether the upregulation of PRMT6 expression can
attenuate the development of cigarette smoke extract (CSE)-induced emphysema.
Further experiments were performed to elucidate the molecular mechanisms
involved.
Materials and
methods: Human lung tissues were obtained
from patients undergoing pneumonectomy for benign pulmonary lesions. BALB/c
mice were treated with lentiviral vectors intratracheally and injected with CSE
three times. The protein expression of PRMT6, H3R2me2a, and H3K4me3 in human
and mouse samples, as well as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X
protein (Bax), and endothelial nitric oxide synthase (eNOS) in mice were
detected in lung homogenates by Western blotting. The mRNA expression of
cyclooxygenase-2, interleukin-6, Bcl-2, Bax, and eNOS in mice was measured by
quantitative real-time polymerase chain reaction.
Results: The expression of PRMT6 was significantly downregulated in the pulmonary
parenchyma in smokers with COPD as well as in mice treated with CSE.
Overexpression of PRMT6 was detected in the CSE + Lenti-PRMT6 group of mice,
which reversed the expression of H3R2me2a and H3K4me3. Inflammation, apoptosis,
and oxidative stress levels were severe in the CSE-treated emphysema mice
compared with the control group, which was inhibited by the overexpression of
PRMT6.
Conclusion: The overexpression of PRMT6 might inhibit inflammation, apoptosis, and
oxidative stress in CSE-induced emphysema mediated by H3R2me2a.
Keywords: COPD, cigarette smoke extract, inflammation,
apoptosis, oxidative stress, PRMT6