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

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.