LSM2对慢阻肺气道、肺上皮损伤修复的调控作用研究

炎症和氧化应激及其引发的上皮屏障功能受损是最先发生，同时也是COPD病变进展的关键。然而，目前临床上依然缺乏有效修复上皮的手段。LSM2在前体信使RNA（pre-mRNA）剪接和降解等过程中起重要作用，但其在COPD发生发展中的作用未知。我们前期研究发现，在COPD稳定期患者血浆中外泌体LSM2基因和蛋白显著高于健康吸烟人群；LSM2主要表达于气道、肺上皮细胞；烟雾刺激上调LSM2在气道、肺上皮细胞中的表达；敲除Lsm2加重烟熏诱导的小鼠肺部炎症反应和损伤；慢病毒敲减LSM2抑制uPA和SREBP1/SCD1等信号通路，引起线粒体介导的上皮细胞凋亡。因此，我们推测LSM2在肺部炎症、氧化应激及上皮损伤修复中起关键作用。本研究将探讨LSM2在慢阻肺气道、肺上皮损伤修复中的作用及机制，为COPD的防治提供新的关键靶点。

Inflammation and oxidative stress induced epithelial barrier dysfunction is the first step which plays a critical role in the progression of COPD; however, there is still a lack of efficient treatments for the repair of epithelium after injury. U6 snRNA-associated Sm-like protein LSm2 (LSM2) regulates pre-mRNA splicing; however, the role of LSM2 in COPD is not clear. In previous studies, we found that the levels of exosomal LSM2 mRNA and protein from patients with COPD were significantly higher than that from healthy smokers. LSM2 was mainly expressed in the airway and lung epithelial cells, and cigarette smoke significantly upregulated the expression of LSM2. Lsm2 knockout in mice significantly aggravated the smoke-induced lung inflammation and damage. LSM2 knockdown in human airway epithelial cells significantly decreased the cell proliferation by inhibiting urokinase plasminogen activator (uPA) and sterol regulatory element-binding protein-1 (SREBP1)/stearoyl-CoA desaturase 1 (SCD1) pathways. Therefore, we hypothesize that LSM2 plays an important role in lung inflammation, oxidative stress, and the repair of epithelium after injury. Using the LSM2 conditional knockout mice, we propose to study the role of LSM2 in the repair of airway and lung epithelium after injury. Our studies will provide critical targets for the treatment of COPD.