Transcriptome analysis identifies IL24 as an autophagy modulator in PM2.5 caused lung dysfunction

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

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

通信作者："He, X; Li, GP (通讯作者)，Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Chengdu Inst Resp Hlth,Sch Med,Lab Allergy & Preci, Chengdu 610031, Peoples R China.; Li, GP (通讯作者)，ChongQing Med Univ, Chengdu Peoples Hosp Branch 3, Dept Pulm & Crit Care Med, Affiliated Hosp,Natl Clin Res Ctr Resp Dis, Chengdu 610031, Peoples R China.; Xiong, Y (通讯作者)，Sichuan Friendship Hosp, Dept Pulm & Crit Care Med, Chengdu 610000, Peoples R China."

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:000862797900005

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：244

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Transcriptome; IL24; Autophagy; PM2.5; Lung injury

摘要："Background: Evidence suggests that exposure to PM2.5 increased hospitalization and mortality rates of respiratory diseases. However, the potential biomarkers and targets associated with PM2.5-induced lung dysfunction are not fully discovered. Methods: Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and HALLMARK enrichment analysis of the RNA-seq data (Beas-2B cells treated with PM2.5) were applied. Gene set enrichment analysis (GSEA) was performed to identify the biological processes correlated with autophagy. Three gene expression profile datasets (GSE158954, GSE155616 and GSE182199) were downloaded from the Gene Expression Omnibus (GEO) database to identify the potential targets. PM2.5(2.5)-exposed mice were constructed. Real-time qPCR, siRNA transfection, western blot, immunofluorescence, and pathological staining were applied for validation both in vitro and in vivo studies. Results: GO, KEGG and HALLMARK enrichment based on RNA-seq data showed that the differentially expressed genes (DEGs) were associated with autophagy like lysosome and macroautophagy. GSEA analysis revealed that PM2.5 was positively correlated with autophagy-related biological processes compared with control group. Venn diagrams identified IL24 was upregulated in our data as well as in these three datasets (GSE158954, GSE155616 and GSE182199) after PM(2.5 )exposure. Consistent with the analysis, activation of autophagy by PM2.5 was validated in vivo and in vitro. In PM2.5(2.5)-exposed mice, lung pathological changes were observed, including airway inflammation and mucus secretion. The mRNA and protein levels of the key gene, IL24, were significantly increased. Moreover, Bafilomycin A1, the inhibitor of autophagy, inhibited the autophagy and ameliorated lung injury induced by PM2.5. Furthermore, downregulation of IL24 decreased autophagy activity. Meanwhile, IL24 was regulated by mTOR signaling. Conclusions: In summary, we discovered a potential relationship between IL24 and autophagy during PM2.5 exposure. IL24 might be a novel potential biomarker or therapeutic target in PM2.5 caused lung dysfunction through regulation of autophagy."

基金机构："National Natural Science Foundation of China [81970026, 82000029]; Chengdu High-level Key Clinical Specialty Construction Project [ZX20201202020]; Chengdu Science and Technology Bureau [2021-YF09-00102-SN, 2020-YF05-00003-SN]; program for combination of Medical and Engineering of Southwest Jiaotong University [2682021ZTPY007, 2682020ZT8]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (81970026, 82000029) , Chengdu High-level Key Clinical Specialty Construction Project (ZX20201202020) , Chengdu Science and Technology Bureau (2021-YF09-00102-SN, 2020-YF05-00003-SN) , the program for combination of Medical and Engineering of Southwest Jiaotong University (2682021ZTPY007, 2682020ZT8) ."