Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Oxid Med Cell Longev. 2022 May 5;2022:5695005. doi: 10.1155/2022/5695005. eCollection 2022.
MicroRNAs (miRNAs) have been reported in human diseases, in which chronic obstructive pulmonary disease (COPD) is included. Herein, we assessed the role along with the possible mechanisms of miR-150-5p in cigarette smoke- (CS-) induced COPD. The plasma miR-150-5p expression was lower in patients with COPD and acute exacerbation of COPD (AECOPD) and was related to disease diagnosis, disease severity, and lung function. Consistently, exposure to CS for 3 months or 3 days reduced miR-150-5p in the plasma and lung tissues of mice, and CS extract (CSE) inhibited miR-150-5p in human bronchial epithelial cells (HBECs) in a concentration along with time-dependent approach. In vitro, miR-150-5p overexpression decreased the contents of inflammatory factors interleukin- (IL-) 6, IL-8 along with cyclooxygenase-2 (COX-2), and endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP) and promoted cell migrate. Mechanistically, miR-150-5p could bind with the 3'-untranslated region (UTR) of inositol requiring enzyme 1 (IRE1), while IRE1 overexpression obliterated the impacts of miR-150-5p. Besides, N-acetyl-cysteine (NAC) reversed CSE-induced miR-150-5p downregulation and its downstream effects. In vivo, miR-150-5p overexpression counteracted CS-triggered IRE1 upregulation, inflammation, and ER stress in the lung tissues of mice. In conclusion, our findings illustrated that ROS-mediated downregulation of miR-150-5p led to CS-induced COPD by inhibiting IRE1 expression, suggesting to serve as a useful biomarker for diagnosing and treating COPD.
微小 RNA（miRNAs）已在人类疾病中得到报道，其中包括慢性阻塞性肺疾病（COPD）。在此，我们评估了 miR-150-5p 在香烟烟雾（CS）诱导的 COPD 中的作用及其可能的机制。COPD 患者和 COPD 急性加重（AECOPD）患者的血浆 miR-150-5p 表达水平较低，与疾病诊断、疾病严重程度和肺功能有关。一致地，暴露于 CS 3 个月或 3 天会降低小鼠血浆和肺组织中的 miR-150-5p，并且 CS 提取物（CSE）以浓度和时间依赖性方式抑制人支气管上皮细胞（HBECs）中的 miR-150-5p。在体外，miR-150-5p 的过表达降低了炎症因子白细胞介素（IL）-6、IL-8 以及环氧化酶-2（COX-2）和内质网（ER）应激标志物葡萄糖调节蛋白（GRP）78 和 C/-EBP 同源蛋白（CHOP）的含量，并促进细胞迁移。在机制上，miR-150-5p 可以与肌醇需求酶 1（IRE1）的 3'-非翻译区（UTR）结合，而 IRE1 的过表达消除了 miR-150-5p 的影响。此外，N-乙酰半胱氨酸（NAC）逆转了 CSE 诱导的 miR-150-5p 下调及其下游作用。在体内，miR-150-5p 的过表达拮抗了 CS 引发的小鼠肺组织中 IRE1 的上调、炎症和 ER 应激。总之，我们的研究结果表明，ROS 介导的 miR-150-5p 下调通过抑制 IRE1 表达导致 CS 诱导的 COPD，提示其可作为诊断和治疗 COPD 的有用生物标志物。
