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

Yao Liu; Xiang He; Jiliu Liu; Lei Zhang; Anying Xiong; Junyi Wang; Shengbin Liu; Manling Jiang; Li Luo; Ying Xiong; Guoping Li

Ecotoxicology and Environmental Safety (Oct 2022)

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

Yao Liu,
Xiang He,
Jiliu Liu,
Lei Zhang,
Anying Xiong,
Junyi Wang,
Shengbin Liu,
Manling Jiang,
Li Luo,
Ying Xiong,
Guoping Li

Affiliations

Yao Liu: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Xiang He: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Corresponding authors.
Jiliu Liu: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Lei Zhang: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Anying Xiong: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Junyi Wang: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Shengbin Liu: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Manling Jiang: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Li Luo: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Ying Xiong: Department of Pulmonary and Critical Care Medicine, Sichuan Friendship Hospital, Chengdu 610000, China; Corresponding authors.
Guoping Li: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China; Corresponding author at: School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China.

Journal volume & issue: Vol. 244
p. 114039

Abstract

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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-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 PM2.5 exposure. Consistent with the analysis, activation of autophagy by PM2.5 was validated in vivo and in vitro. In PM2.5-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.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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