University Sains Malaysia, Minden, Penang 11800, Malaysia.
National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Sci Total Environ. 2024 Nov 25;953:176017. doi: 10.1016/j.scitotenv.2024.176017. Epub 2024 Sep 3.
The extensive use of plastic products has exacerbated micro/nanoplastic (MPs/NPs) pollution in the atmosphere, increasing the incidence of respiratory diseases and lung cancer. This study investigates the uptake and cytotoxicity mechanisms of polystyrene (PS) NPs in human lung epithelial cells. Transcriptional analysis revealed significant changes in cell adhesion pathways following PS-NPs exposure. Integrin α5β1-mediated endocytosis was identified as a key promoter of PS-NPs entry into lung epithelial cells. Overexpression of integrin α5β1 enhanced PS-NPs internalization, exacerbating mitochondrial Ca2+ dysfunction and depolarization, which induced reactive oxygen species (ROS) production. Mitochondrial dysfunction triggered by PS-NPs led to oxidative damage, inflammation, DNA damage, and necrosis, contributing to lung diseases. This study elucidates the molecular mechanism by which integrin α5β1 facilitates PS-NPs internalization and enhances its cytotoxicity, offering new insights into potential therapeutic targets for microplastic-induced lung diseases.
塑料制品的广泛使用加剧了大气中的微/纳米塑料（MPs/NPs）污染，增加了呼吸道疾病和肺癌的发病率。本研究探讨了聚苯乙烯（PS）纳米颗粒在人肺上皮细胞中的摄取和细胞毒性机制。转录分析显示，PS-NPs 暴露后细胞黏附途径发生显著变化。整合素 α5β1 介导的内吞作用被确定为 PS-NPs 进入肺上皮细胞的关键促进剂。整合素 α5β1 的过表达增强了 PS-NPs 的内化，加剧了线粒体 Ca2+功能障碍和去极化，从而诱导活性氧（ROS）的产生。PS-NPs 引起的线粒体功能障碍导致氧化损伤、炎症、DNA 损伤和坏死，导致肺部疾病。本研究阐明了整合素 α5β1 促进 PS-NPs 内化及其细胞毒性增强的分子机制，为微塑料诱导的肺部疾病的潜在治疗靶点提供了新的见解。
