上皮-间质转换
肺纤维化
CDH1
波形蛋白
钙粘蛋白
癌症研究
纤维化
间充质干细胞
化学
信使核糖核酸
细胞生物学
生物
医学
下调和上调
病理
细胞
基因
免疫组织化学
生物化学
作者
Jie Ning,DU Hai-rong,Yaling Zhang,Qingping Liu,Tao Jiang,Yaxian Pang,Xiaochen Tian,Liqun Yan,Yujie Niu,Rong Zhang
标识
DOI:10.1093/toxsci/kfab133
摘要
The association between ambient airborne fine particulate matter (PM2.5) exposure and respiratory diseases has been investigated in epidemiological studies. To explore the potential mechanism of PM2.5-induced pulmonary fibrosis, 60 mice were divided into 3 groups to expose to different levels of PM2.5 for 8 and 16 weeks: filtered air, unfiltered air, and concentrated PM2.5 air, respectively. BEAS-2B cells were treated with 0, 25, 50, and 100 μg/ml PM2.5 for 24 h. The biomarkers of pulmonary fibrosis, epithelial-mesenchymal transition, N6-methyladenosine (m6A) modification, and metabolism of mRNAs were detected to characterize the effect of PM2.5 exposure. The results illustrated that PM2.5 exposure induced pathological alteration and pulmonary fibrosis in mice. The expression of E-cadherin was decreased whereas vimentin and N-cadherin expression were increased in a dose- and time-dependent manner after PM2.5 exposure. Mechanistically, PM2.5 exposure increased the levels of METTL3-mediated m6A modification of CDH1 mRNA. As a target gene of miR-494-3p, YTHDF2 was upregulated by miR-494-3p down-regulation and then recognized m6A-modified CDH1 mRNA to inhibit the E-cad expression, consequently induced the EMT progression after PM2.5 exposure. Our study indicated that PM2.5 exposure triggered EMT progression to promote the pulmonary fibrosis via miR-494-3p/YTHDF2 recognized and METTL3 mediated m6A modification.
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