DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen.
DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen.
复制标题
DRP1介导的线粒体裂变调节对过敏原的肺上皮反应。
DOI：
10.3390/ijms222011125
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发表时间：
2021-10-15
影响因子：
5.6
通讯作者：
Anathy V
中科院分区：
文献类型：
--
作者：
Bruno SR;Kumar A;Mark ZF;Chandrasekaran R;Nakada E;Chamberlain N;Mihavics B;Walzer J;Cahoon J;Dixon AE;Cunniff B;Anathy V
线粒体调节无数的细胞功能。气道上皮细胞内线粒体控制的失调与哮喘患者对过敏原的促炎反应有关。由于其多面性，线粒体结构必须通过裂变和融合进行严格调节。动力蛋白相关蛋白1（DRP1）是线粒体分裂的关键驱动因素。在过敏性哮喘中，气道上皮线粒体变小，结构改变。然而，DRP1介导的线粒体分裂在上皮对过敏原的反应中的作用尚未完全阐明。我们使用人支气管上皮细胞系（HBEC），原代小鼠气管上皮细胞（MTEC）和肺上皮细胞中的条件性DRP 1消融来研究线粒体分裂对体外和体内对屋尘螨（HDM）的促炎反应的影响。我们的数据表明，在HDM攻击后，气道上皮细胞中的线粒体分裂迅速上调，并先于促炎细胞因子和趋化因子的产生。此外，肺上皮细胞中Drp1的缺失导致体外响应HDM的分裂减少和促炎信号传导增强，以及体内气道高反应性（AHR）、炎症、差异粘蛋白转录和上皮细胞死亡增强。因此，线粒体分裂调节肺上皮对HDM的促炎反应。
Mitochondria regulate a myriad of cellular functions. Dysregulation of mitochondrial control within airway epithelial cells has been implicated in the pro-inflammatory response to allergens in asthma patients. Because of their multifaceted nature, mitochondrial structure must be tightly regulated through fission and fusion. Dynamin Related Protein 1 (DRP1) is a key driver of mitochondrial fission. During allergic asthma, airway epithelial mitochondria appear smaller and structurally altered. The role of DRP1-mediated mitochondrial fission, however, has not been fully elucidated in epithelial response to allergens. We used a Human Bronchial Epithelial Cell line (HBECs), primary Mouse Tracheal Epithelial Cells (MTECs), and conditional DRP1 ablation in lung epithelial cells to investigate the impact of mitochondrial fission on the pro-inflammatory response to house dust mite (HDM) in vitro and in vivo. Our data suggest that, following HDM challenge, mitochondrial fission is rapidly upregulated in airway epithelial cells and precedes production of pro-inflammatory cytokines and chemokines. Further, deletion of Drp1 in lung epithelial cells leads to decreased fission and enhanced pro-inflammatory signaling in response to HDM in vitro, as well as enhanced airway hyper-responsiveness (AHR), inflammation, differential mucin transcription, and epithelial cell death in vivo. Mitochondrial fission, therefore, regulates the lung epithelial pro-inflammatory response to HDM.
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影响因子：
4.6
作者：
Antony, P. M. A.;Kondratyeva, O.;Diederich, N. J.
通讯作者：
Diederich, N. J.
DOI：
10.1152/ajplung.00232.2019
发表时间：
2019-09-01
影响因子：
4.9
作者：
Chan, Yik Lung;Wang, Baoming;Oliver, Brian Gregory George
通讯作者：
Oliver, Brian Gregory George
影响因子：
21.3
作者：
Bleazard, W;McCaffery, JM;Shaw, JM
通讯作者：
Shaw, JM
DOI：
10.1152/ajplung.00155.2013
发表时间：
2014-05-01
影响因子：
4.9
作者：
Aravamudan, Bharathi;Kiel, Alexander;Prakash, Y. S.
通讯作者：
Prakash, Y. S.
影响因子：
14.2
作者：
de Marco, Roberto;Marcon, Alessandro;Janson, Christer
通讯作者：
Janson, Christer