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miR-20b suppresses mitochondrial dysfunction–mediated apoptosis to alleviate hyperoxia-induced acute lung injury by directly targeting MFN1 and MFN2
Acta Biochimica et Biophysica Sinica ( IF 3.7 ) Pub Date : 2020-12-21 , DOI: 10.1093/abbs/gmaa161
Genhua Mu 1, 2 , Yijun Deng 2 , Zhongqian Lu 2 , Xing Li 2 , Yanbin Chen 1
Affiliation  

Supplemental oxygen is commonly used to treat severe respiratory failure, while prolonged exposure to hyperoxia can induce acute lung injury characterized by the accumulation of reactive oxygen species (ROS) and pulmonary inflammation. Dysregulation of microRNAs contributes to multiple diseases, including hyperoxia-induced acute lung injury (HALI). In this study, we explored the roles of miR-20b in mediating the response of type II alveolar epithelial cells (ACE IIs) to hyperoxia and the potential underlying mechanisms. We found that miR-20b was significantly decreased in the lung tissues of HALI models and H2O2-treated ACE IIs. Hyperoxia induced the release of TNF-α, decreased the mitochondrial membrane potential, and led to excessive ROS production and cell apoptosis. Overexpression of miR-20b suppressed the hyperoxia-induced biological effects in ACE IIs. miR-20b negatively regulated the expression levels of Mitofusin 1 (MFN1) and MFN2, the two key proteins of mitochondrial fusion, via complementarily binding to the 3ʹ-untranslated regions of mRNAs. Furthermore, both in vivo and in vitro, upregulation of MFN1 and MFN2 aggravated lung damage and cell apoptosis that were alleviated by miR-20b overexpression. These results provided new insights into the involvement of the miR-20b/MFN1/2 signaling pathway in HALI.

中文翻译:

miR-20b通过直接靶向MFN1和MFN2抑制线粒体功能障碍介导的细胞凋亡,从而减轻高氧血症引起的急性肺损伤

补充氧气通常用于治疗严重的呼吸衰竭,而长时间暴露于高氧会导致急性肺损伤,其特征在于活性氧(ROS)的积累和肺部炎症。microRNA的失调导致多种疾病,包括高氧诱导的急性肺损伤(HALI)。在这项研究中,我们探讨了miR-20b在介导II型肺泡上皮细胞(ACE IIs)对高氧反应和潜在潜在机制中的作用。我们发现miR-20b在HALI模型和H 2 O 2的肺组织中显着降低处理的ACE II。高氧诱导TNF-α的释放,降低线粒体膜电位,并导致过多的ROS产生和细胞凋亡。miR-20b的过表达抑制了ACE IIs中高氧诱导的生物学效应。miR-20b通过互补结合mRNA的3′-非翻译区,负调控线粒体融合的两个关键蛋白-线粒体蛋白1(MFN1)和MFN2的表达水平。此外,在体内体外,miR-20b过表达缓解了MFN1和MFN2的上调加重了肺损伤和细胞凋亡。这些结果为miR-20b / MFN1 / 2信号通路参与HALI提供了新的见识。
更新日期:2020-12-22
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