Methyltransferase-like 3 leads to lung injury by up-regulation of interleukin 24 through N6-methyladenosine-dependent mRNA stability and translation efficiency in mice exposed to fine particulate matter 2.5

作者全名:"He, Xiang; Zhang, Lei; Liu, Shengbin; Wang, Junyi; Liu, Yao; Xiong, Anying; Jiang, Manling; Luo, Li; Ying, Xiong; Li, Guoping"

作者地址:"[He, Xiang; Zhang, Lei; Liu, Shengbin; Wang, Junyi; Liu, Yao; Xiong, Anying; Jiang, Manling; Luo, Li; Li, Guoping] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Chengdu Inst Resp Hlth, Lab Allergy & Precis Med,Affiliated Hosp, Chengdu 610031, Peoples R China; [He, Xiang; Zhang, Lei; Liu, Shengbin; Wang, Junyi; Liu, Yao; Xiong, Anying; Jiang, Manling; Luo, Li; Li, Guoping] ChongQing Med Univ, Natl Clin Res Ctr Resp Dis, Dept Pulm & Crit Care Med, Affiliated Hosp,Chengdu Peoples Hosp Branch 3, Chengdu 610031, Peoples R China; [Ying, Xiong] Sichuan Friendship Hosp, Dept Pulm & Crit Care Med, Chengdu 610000, Peoples R China"

通信作者:"Li, GP (通讯作者),Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Chengdu Inst Resp Hlth, Lab Allergy & Precis Med,Affiliated Hosp, Chengdu 610031, Peoples R China."

来源:ENVIRONMENTAL POLLUTION

ESI学科分类:ENVIRONMENT/ECOLOGY

WOS号:WOS:000817826300001

JCR分区:Q1

影响因子:8.9

年份:2022

卷号:308

期号: 

开始页: 

结束页: 

文献类型:Article

关键词:PM2; 5; METTL3; YTHDF1; IL24; Epigenetics; Lung injury

摘要:"Fine particulate matter 2.5 (PM2.5) exposure leads to the progress of pulmonary disease. It has been reported that N6-methyladenosine (m6A) modification was involved in various biological processes and diseases. However, the critical role of m6A modification in pulmonary disease during PM2.5 exposure remains elusive. Here, we revealed that lung inflammation and mucus production caused by PM2.5 were associated with m6A modification. Both in vivo and in vitro assays demonstrated that PM2.5 exposure elevated the total level of m6A modification as well as the methyltransferase like 3 (METTL3) expression. Integration analysis of m6A RNA immunoprecipitation-seq (meRIP-seq) and RNA-seq discovered that METTL3 up-regulated the expression level and the m6A modification of Interleukin 24 (IL24). Importantly, we explored that the stability of IL24 mRNA was enhanced due to the increased m6A modification. Moreover, the data from qRT-PCR showed that PM2.5 also increased YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) expression, and the up-regulated YTHDF1 augmented IL24 mRNA translation efficiency. Down-regulation of Mettl3 reduced Il24 expression and ameliorated the pulmonary inflammation and mucus secretion in mice exposed to PM2.5. Taken together, our finding provided a comprehensive insight for revealing the significant role of m6A regulators in the lung injury via METTL3/YTHDF1-coupled epitranscriptomal regulation of IL24."

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