MicroRNAs associated with smoking-induced pulmonary emphysema in senescence marker protein-30 knockout mice

吸烟是慢性阻塞性肺疾病（COPD）最重要的病因，但其发病机制尚不完全明确。我们之前报道过衰老标记蛋白30敲除（SMP30-KO）小鼠可用于研究香烟烟雾引起的肺气肿。此外，我们已经证明miR-146a在COPD的异常炎症反应中起致病作用。在暴露于稀释的香烟烟雾或新鲜空气2周期间，维生素c控制的SMP30-KO在第1天和第8天鼻内给予miR-146a抑制剂。miR-146a抑制剂和烟雾暴露小鼠的BALF中总细胞和淋巴细胞数量均增加。暴露于miR-146a抑制剂和香烟烟雾中，PGE2的产生和COX-2的表达也显著增加。总之，miR-146a似乎在香烟烟雾暴露的COPD小鼠模型中的异常炎症反应中发挥了致病作用。

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), but the mechanisms of pathogenesis are incompletely defined. We have previously reported that senescence marker protein-30 knockout (SMP30-KO) mice can be useful for investigating cigarette smoke-induced pulmonary emphysema. Moreover, we have already shown that miR-146a plays a pathogenetic role in the abnormal inflammatory response in COPD.Vitamin C-controlled SMP30-KO were given miR-146a inhibitor on day 1 and 8 intranasally during exposure to either diluted cigarette smoke or fresh air for 2 weeks. Total cell and lymphocyte numbers were increased in the BALF of both miR-146a inhibitor and smoke exposed mice. PGE2 production and COX-2 expression were also increased significantly higher by exposure both miR-146a inhibitor and cigarette smoke.In conclusion, miR-146a appears to play a pathogenetic role in the abnormal inflammatory response in a cigarette smoke-exposed murine model of COPD.