MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema.
MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema.
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MTMR14 作为炎症和肺气肿的调节剂减轻慢性阻塞性肺疾病
DOI：
10.1155/2022/9300269
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发表时间：
2022
影响因子：
--
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Gu Y;Chen J;Huang Q;Zhan Y;Wang T;Wu J;Zhao J;Zeng Z;Lv Y;Xiao C;Xie J
肺部结构细胞中广泛的炎症和细胞凋亡是慢性阻塞性肺疾病（COPD）的进展和发病机制的原因。肌管蛋白相关蛋白 14 (MTMR14) 已被证明参与多种生物过程，包括细胞凋亡、炎症和自噬。尽管如此，MTMR14 在 COPD 中的作用仍然难以捉摸。在本研究中，我们探讨了MTMR14在人肺组织中的表达，并研究了过表达的MTMR14对体外和体内COPD模型的影响。此外，基于线粒体功能和线粒体自噬稳态，探讨了 MTMR14 缓解 COPD 的可能机制之一。结果显示，与对照组相比，COPD 患者肺部的 MTMR14 表达降低。 MTMR14 过表达可抑制香烟烟雾提取物诱导的炎症和细胞凋亡，并在体外改善线粒体功能和线粒体自噬。在COPD模型小鼠中进行了进一步验证。 MTMR14 过表达可抑制肺部炎症，降低支气管肺泡灌洗液中 IL-6 和 KC 的水平，并预防肺气肿和肺功能下降。此外，MTMR14过表达在一定程度上改善了线粒体功能和线粒体自噬。总的来说，我们的数据支持 MTMR14 参与 COPD 发病机制的假设。改善线粒体功能和线粒体自噬稳态可能是 MTMR14 缓解 COPD 的机制之一，并可能成为 COPD 的新治疗靶点。
Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro. Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD.
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影响因子：
3.5
作者：
Li, Zhaodong;Rong, Li;Li, Xiang
通讯作者：
Li, Xiang
影响因子：
10
作者：
Ganesan S;Unger BL;Comstock AT;Angel KA;Mancuso P;Martinez FJ;Sajjan US
通讯作者：
Sajjan US
影响因子：
5.8
作者：
Demedts, Ingel K.;Demoor, Tine;Bracke, Ken R.;Joos, Guy F.;Brusselle, Guy G.
通讯作者：
Brusselle, Guy G.
影响因子：
3.2
作者：
Franciosi, LG;Page, CP;Della Pasqua, OE
通讯作者：
Della Pasqua, OE
影响因子：
15.9
作者：
Mizumura, Kenji;Cloonan, Suzanne M.;Choi, Augustine M. K.
通讯作者：
Choi, Augustine M. K.