DLEU2-TRIM13在ERS条件下通过内质网自噬调控COPD肺泡上皮细胞损伤的作用机制研究

COPD作为四大慢病之一成为重要的公共卫生问题，云南地区的COPD负担尤为严重。我们首次发现LncRNA Dleu2及TRIM13在COPD患者的肺泡上皮细胞中表达下调，并且在CSE诱导的AECII的ERS模型中TRIM13表达亦下调。据此，本项目拟构建ERS条件下AECII细胞自噬模型，研究过表达/干扰TRIM13对AECII细胞自噬负调控PI3K-Akt-mTOR信号通路、自噬正调控AMPK-mTOR信号通路的影响；观察过表达/干扰TRIM13前后细胞内自噬体、自噬溶酶体等超微结构以及TRIM13亚细胞分布的变化，进一步探寻TRIM13对内质网自噬的影响；观察过表达/干扰LncRNA Dleu2后对TRIM13及其下游信号通路的影响，从而最终阐明DLEU2-TRIM13在ERS下通过内质网自噬调控COPD肺泡上皮细胞损伤的作用及分子生物学机制，为COPD的诊断与治疗提供新证据。

As one of the four major chronic diseases, COPD has been a critical public health problem, and the burden from COPD in Yunnan region is particularly serious. We found for the first time that the expression of LncRNA Dleu2 and TRIM13 is down-regulated in alveolar epithelial cells of COPD patients, and the expression of TRIM13 is also down-regulated in the Endoplasmic Reticulum Stress (ERS) model of type II alveolar epithelial cells (AECII) induced by CSE. Accordingly, we plan to construct an AEC II cell autophagy model under ERS conditions, to study the effects of overexpression / interference of TRIM13 on the PI3K-Akt-mTOR signaling pathway which negatively regulate autophagy and AMPK-mTOR signaling pathway which positively regulate autophagy in the AEC II cells; to observe the changes of intracellular autophagosomes, autophagolysosomes and other ultrastructures and TRIM13 sub-cellular distribution before and after overexpression / interference with TRIM13, and to further explore the effect of TRIM13 on endoplasmic reticulum autophagy; and to observe the effect of overexpressing / interfering with LncRNA Dleu2 on TRIM13 and its downstream signaling pathways, so as to finally reveal and clarify the role and molecular biology mechanism of DLEU2-TRIM13 in regulating the injury of COPD alveolar epithelial cells through endoplasmic reticulum autophagy under ERS conditions, and thus it will provide new evidence for the diagnosis and treatment of COPD.