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Transcriptome analysis identifies IL24 as an autophagy modulator in PM2.5 caused lung dysfunction
Yao Liu1, Xiang He2, Jiliu Liu1
1School 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.
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.
Insights
Exposure to fine particulate matter (PM2.5) triggers lung dysfunction. This study identifies IL24 as a key gene involved in PM2.5-induced autophagy, suggesting it as a potential therapeutic target for respiratory diseases.
Area of Science:
- Environmental Health
- Molecular Biology
- Pulmonology
Background:
- Particulate matter (PM2.5) exposure is linked to increased respiratory disease hospitalization and mortality.
- The specific biomarkers and molecular targets underlying PM2.5-induced lung dysfunction remain incompletely understood.
Purpose of the Study:
- To investigate the molecular mechanisms and identify potential biomarkers associated with PM2.5-induced lung dysfunction.
- To explore the role of autophagy in PM2.5-mediated lung injury.
Main Methods:
- RNA-sequencing (RNA-seq) with Gene Ontology (GO), KEGG, and HALLMARK enrichment analyses were performed on PM2.5-treated Beas-2B cells.
- Gene Set Enrichment Analysis (GSEA) identified autophagy-related biological processes.
- Validation involved analyzing GEO datasets (GSE158954, GSE155616, GSE182199), constructing PM2.5-exposed mouse models, and employing techniques like qPCR, western blot, and immunofluorescence.
Main Results:
- PM2.5 exposure significantly upregulated differentially expressed genes associated with autophagy, including lysosome and macroautophagy.
- The gene IL24 was consistently upregulated across RNA-seq data and public datasets following PM2.5 exposure.
- PM2.5 activated autophagy in vitro and in vivo, leading to lung inflammation and mucus secretion. IL24 levels increased, and autophagy inhibition ameliorated lung injury.
Conclusions:
- A significant link between IL24 and autophagy was identified in the context of PM2.5 exposure.
- IL24 may serve as a novel biomarker or therapeutic target for PM2.5-induced lung dysfunction via modulation of autophagy.
