Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Ecotoxicol Environ Saf. 2023 Apr 1;254:114750. doi: 10.1016/j.ecoenv.2023.114750. Epub 2023 Mar 9.
Fine particulate matter (PM) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM-induced airway obstruction. RNA sequencing revealed that acute PM exposure altered the expression profiles of 2904 exosomal circRNAs. Among them, exosomal hsa_circ_0029069 (spliced from CLIP1, thus termed circCLIP1 hereafter) with a loop structure was upregulated by PM exposure and mainly encapsulated in exosomes. Then, the biological functions and the underlying mechanisms were explored by Western blot, RNA immunoprecipitation and RNA pull-down, etc. Phenotypically, exosomal circCLIP1 entered recipient cells, inducing mucus secretion in recipient HBE cells and contractility of sensitive HBSMCs. Mechanistically, circCLIP1 was upregulated by METTL3-mediated N-methyladenine (mA) modification in PM-treated producer HBE cells and exosomes, then enhancing the expression of SEPT10 in recipient HBE cells and sensitive HBSMCs. Our study revealed that exosomal circCLIP1 played a critical role in PM-induced airway obstruction and provided a new potential biomarker for the assessment of PM-related adverse effects.
细颗粒物（PM）暴露与气道阻塞相关，但具体机制尚未完全阐明。本研究旨在探讨气道上皮细胞与气道平滑肌细胞之间外泌体环状 RNA（circRNA）介导的通讯在 PM 诱导的气道阻塞中的作用。RNA 测序显示，急性 PM 暴露改变了 2904 种外泌体 circRNA 的表达谱。其中，PM 暴露上调了具有环状结构的外泌体 hsa_circ_0029069（来源于 CLIP1，因此称为 circCLIP1），并主要包裹在 exosomes 中。然后，通过 Western blot、RNA 免疫沉淀和 RNA 下拉等方法探索了其生物学功能和潜在机制。表型上，外泌体 circCLIP1 进入受体细胞，诱导受体 HBE 细胞中粘液分泌和敏感 HBSMCs 的收缩。机制上，PM 处理的供体细胞中 METTL3 介导的 N6-甲基腺苷（m6A）修饰上调了 circCLIP1，随后增强了受体 HBE 细胞和敏感 HBSMCs 中 SEPT10 的表达。本研究揭示了外泌体 circCLIP1 在 PM 诱导的气道阻塞中的关键作用，并为评估 PM 相关不良效应提供了一个新的潜在生物标志物。
