Particulate matter exposure-induced cholesterol metabolism dysregulation in lung epithelial cells

Particulate matter (PM) poses a significant threat to human health, yet its systemic impact on molecular networks and cellular toxicity remains poorly understood. RNA sequencing was employed to explore the molecular mechanisms of micrometer-sized PMs obtained from air near the Yellow River on mink lung epithelial cells. PM particles were first characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectra (IR) to examine morphology and elemental components. Then, the cellular toxicity of PM was examined using the CCK8 method. Results of gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were confirmed using qRT-PCR of cholesterol homeostasis-related genes and free cholesterol measurements. PM exhibited dose-dependent inhibition of proliferation. Bioinformatics analysis indicated that 190 downregulated and 56 upregulated genes were identified after high-dose exposure to PM particles. The cholesterol metabolism pathway was substantially downregulated. The intrinsic mechanism driving the dysfunction of cholesterol metabolism was identified as oxidative stress, confirmed by measurements of reactive oxygen species (ROS), mitochondrial membrane potential, and the characterization of GSSG/GSH and NADP/NADPH ratios. The study highlights the link between PM-induced oxidative stress, impaired cholesterol homeostasis, and potential respiratory diseases, offering new insights into PM's physiological impact on lung cells.