Nix/BNIP3L-dependent mitophagy accounts for airway epithelial cell injury induced by cigarette smoke
Nix/BNIP3L-dependent mitophagy accounts for airway epithelial cell injury induced by cigarette smoke
复制标题
Nix/BNIP3L-依赖性线粒体自噬导致香烟烟雾引起的气道上皮细胞损伤
DOI：
10.1002/jcp.28117
复制
发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Zhang, Jie
中科院分区：
文献类型：
--
作者：
Zhang, Ming;Shi, Rong;Zhang, Jie
香烟烟雾诱导的气道上皮细胞线粒体自噬是慢性阻塞性肺疾病（COPD）发病的重要机制。线粒体蛋白Nix（也称为BNIP3L）是一种选择性自噬受体，参与多种人类疾病。然而，Nix在COPD发展过程中气道上皮细胞损伤中的作用知之甚少。本研究的目的是研究Nix对暴露于香烟烟雾提取物（CSE）的气道上皮细胞线粒体自噬和线粒体功能的影响。本研究发现CSE可增加气道上皮细胞Nix蛋白的表达，诱导线粒体自噬。在7.5%CSE刺激的气道上皮细胞中，Nix siRNA能显著抑制线粒体自噬，减轻线粒体功能障碍和细胞损伤。相反，当气道上皮细胞与7.5%CSE孵育时，Nix过表达增强线粒体自噬，加重线粒体功能障碍和细胞损伤。这些数据表明，Nix依赖性线粒体自噬促进了香烟烟雾诱导的气道上皮细胞和线粒体损伤，并可能参与了COPD和其他香烟烟雾相关疾病的发病机制。
Cigarette smoke-induced airway epithelial cell mitophagy is an important mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Mitochondrial protein Nix (also known as BNIP3L) is a selective autophagy receptor and participates in several human diseases. However, little is known about the role of Nix in airway epithelial cell injury during the development of COPD. The aim of the present study is to investigate the effects of Nix on mitophagy and mitochondrial function in airway epithelial cells exposed to cigarette smoke extract (CSE). Our present study has found that CSE could increase Nix protein expression and induce mitophagy in airway epithelial cells. And Nix siRNA significantly inhibited mitophagy and attenuated mitochondrial dysfunction and cell injury when airway epithelial cells were stimulated with 7.5% CSE. In contrast, Nix overexpression enhanced mitophagy and aggravated mitochondrial dysfunction and cell injury when airway epithelial cells were incubated with 7.5% CSE. These data suggest that Nix-dependent mitophagy promotes airway epithelial cell and mitochondria injury induced by cigarette smoke, and may be involved in the pathogenesis of COPD and other cigarette smoke-associated diseases.