Abstract：
Fine particulate matter (PM2.5) 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 PM2.5-induced airway obstruction. RNA sequencing revealed that acute PM2.5 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 PM2.5 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 N6-methyladenine (m6A) modification in PM2.5-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 PM2.5-induced airway obstruction and provided a new potential biomarker for the assessment of PM2.5-related adverse effects.
摘要：
细颗粒物（PM2.5）暴露与气道阻塞相关，但机制仍有待充分阐明。我们的目的是研究外泌体环状RNA（circRNAs）介导的气道上皮细胞和气道平滑肌细胞之间的通讯在PM2.5诱导的气道阻塞中的作用。RNA测序显示，急性PM2.5暴露改变了2904个外泌体circRNAs的表达谱。其中,具有环状结构的外泌体hsa_circ_0029069（剪接自CLIP1，以下称为circCLIP1）被PM2.5暴露上调，主要被包裹在外泌体中。然后，通过Westernblot探索生物学功能和潜在机制，RNA免疫沉淀和RNA下拉，等。表型，外泌体circCLIP1进入受体细胞，诱导受体HBE细胞粘液分泌和敏感HBSMC的收缩性。机械上,在PM2.5处理的生产者HBE细胞和外来体中，通过METTL3介导的N6-甲基腺嘌呤（m6A）修饰上调circCLIP1，然后增强受体HBE细胞和敏感HBSMC中SEPT10的表达。我们的研究表明，外泌体circCLIP1在PM2.5诱导的气道阻塞中起着关键作用，并为评估PM2.5相关的不良反应提供了新的潜在生物标志物。
