肌管蛋白相关蛋白14介导的线粒体自噬在慢性阻塞性肺疾病气道炎症中的作用研究

The role of MTMR14-mediated mitophagy in airway inflammation in COPD

目的探讨肌管蛋白相关蛋白14(MTMR14)介导的线粒体自噬在慢性阻塞性肺疾病(COPD气道炎症中的作用。方法选择2020年12月至2021年12月在本院胸外科因医疗原因接受手术的患者作为研究对象。根据肺功能和吸烟史将受试者分为2组:对照组和COPD组。通过免疫组化和免疫印迹检测MTMR14在人肺组织中的表达。分别采用香烟烟雾提取物(CSE)处理人气道上皮细胞系NuLi-1和小鼠来模拟COPD,并研究了过表达的MTMR14对体外和体内COPD模型的影响。结果与对照组相比,COPD患者肺部的MTMR14表达降低。MTMR14过表达抑制CSE诱导的细胞活力降低、线粒体氧化应激和炎症,并在体外改善线粒体功能和线粒体自噬。MTMR14过表达抑制COPD小鼠肺部炎症细胞浸润、间质水肿和充血,并降低血清IL-6和IL-8水平。此外,MTMR14过表达在一定程度上改善了COPD小鼠肺组织线粒体功能,抑制线粒体自噬过度激活。结论MTMR14过表达减轻COPD的炎症和肺气肿,这在一定程度上取决于线粒体功能和线粒体自噬的调节。

Objective To investigate the role of myotubulin-related protein 14(MTMR14)-mediated mitophagy in airway inflammation in chronic obstructive pulmonary disease(COPD).Methods Participants who underwent surgery for medical reasons in the department of thoracic surgery of our hospital from December 2020 to December 2021 were selected and assigned to control and COPD group according to lung function and smoking history.Expression of MTMR14 in human lung tissue was detected by immunohistochemistry and immunoblotting.The human airway epithelial cell line NuLi-1 and mice were given cigarette smoke extract(CSE)to simulate COPD,respectively,and the effect of overexpressed MTMR14 on COPD models in vitro and in vivo was investigated.Results MTMR14 expression was reduced in the lungs of COPD patients compared with that of the control group.MTMR14 overexpression inhibited CSE-induced decrease in cell viability,mitochondrial oxidative stress and inflammation,and improved mitochondrial function and mitophagy in vitro.Further validation was performed in COPD model mice.MTMR14 overexpression inhibited lung inflammatory cell infiltration,interstitial edema and congestion,and decreased serum IL-6 and IL-8 levels in COPD mice.In addition,MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent and inhibited the excessive activation of mitophagy.Conclusions MTMR14 overexpression alleviates inflammation and emphysema in COPD,which in part depends on the regulation of mitochondrial function and mitophagy.