关键词:

肌管蛋白相关蛋白14, 线粒体自噬, 慢性阻塞性肺疾病, 炎症

Abstract:

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 im⁃ proved 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.

Key words:

"> myotubularin related protein 14, mitophagy, chronic obstructive pulmonary disease, inflammation