circRNA-0026344及外泌体介导自噬与上皮-成纤维细胞cross-talk在吸烟所致慢性阻塞性肺病中作用机制研究

吸烟是引起COPD的主要原因之一，但其发病机制尚不清楚。环状RNA对微小RNA调控及外泌体在环境有害因素所致机体损害中作用机制的研究报道甚少。本项目在率先发现circRNA_0026344可吸附miR-21等结果基础上，拟分别通过香烟烟雾抽提物（CSE）处理肺泡和支气管上皮原代细胞及细胞系、用供体支气管上皮细胞的外泌体或共培养等处理受体支气管成纤维细胞的细胞实验；CS慢性处理对野生型和miR-21-/-小鼠发生COPD情况的动物实验；上调circRNA_0026344和下调miR-21及交互作用对其影响；以及不同程度吸烟人群的队列研究，在细胞、动物和人群三层次系统深入地探讨circRNA_0026344及外泌体介导自噬与上皮-成纤维细胞cross-talk在吸烟所致COPD中作用机制。以揭示吸烟引起COPD的部分分子机制，为寻找吸烟所致危害的早期生物标志和发现新的防治措施提供科学依据。

Cigarette smoking is one of the main factors to chronic obstructive pulmonary disease (COPD), however, its molecular mechanisms remain unclear. There are few publishes about the mechanisms of circular RNA regulating microRNA and exosome in body damages induced by environmental harmful factors. On the basis of our results about circRNA_0026344 sponging miR-21, we are going to investigate the mechanisms of autophagy and epithelium-fibroblast cross-talk mediated by circRNA_0026344 and exosome in cigarette smoking-induced COPD using following experiments: Alveolar and bronchial epithelial cells were treated by cigarette smoking extract (CSE), the bronchial fibroblasts were co-cultured and treated with CSE-exposed bronchial epithelial cells and their exosomes. The wild type and miR-21-/- mice were chronically treated by cigarette smoke. We further investigated the effects of circRNA_0026344 up-regulation and miR-21down-regulation, as well as their interactions, on these experiments. Moreover, we conducted a population cohort study of different smoking levels. Our results will reveal some molecular mechanisms of cigarette smoking-induced COPD, which will provide scientific basis to find early biomarkers and novel measures of preventing and treating the hazards caused by smoking.