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

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2026-03-01 Epub Date: 2025-10-14 DOI:10.1016/j.tiv.2025.106164

Huanxiang Li , Yimin Li , Xiaozhen Wang , Zhiqian Zhong , Yadang Kuang , Jiaxuan Huang

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引用次数: 0

Abstract

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.

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颗粒物暴露诱导的肺上皮细胞胆固醇代谢失调。

颗粒物（PM）对人类健康构成重大威胁，但其对分子网络和细胞毒性的系统性影响仍知之甚少。采用RNA测序的方法，探讨了从黄河附近空气中获得的微米大小的pmms对水貂肺上皮细胞的分子机制。首先使用扫描电子显微镜（SEM）， x射线光电子能谱（XPS）和红外光谱（IR）来检测PM颗粒的形态和元素成分。然后用CCK8法检测PM的细胞毒性。基因本体（GO）分析和基因集富集分析（GSEA）结果通过胆固醇稳态相关基因的qRT-PCR和游离胆固醇测量得到证实。PM表现出剂量依赖性的增殖抑制作用。生物信息学分析表明，高剂量PM暴露后，共鉴定出190个下调基因和56个上调基因。胆固醇代谢途径明显下调。通过测量活性氧（ROS）、线粒体膜电位以及GSSG/GSH和NADP/NADPH比值，我们确定了驱动胆固醇代谢功能障碍的内在机制是氧化应激。该研究强调了PM诱导的氧化应激、胆固醇稳态受损和潜在呼吸系统疾病之间的联系，为PM对肺细胞的生理影响提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.