Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
Am J Physiol Lung Cell Mol Physiol. 2019 Apr 1;316(4):L621-L629. doi: 10.1152/ajplung.00436.2018. Epub 2019 Jan 17.
Chronic obstructive pulmonary disease (COPD) is a common chronic airway inflammatory disease. MicroRNAs are shown to be involved in the regulation of inflammation. We investigated the role of microRNA-29b (miR-29b) in the airway inflammation in COPD. The expression of miR-29b in the lung and plasma was examined. The target of miR-29b, bromodomain protein 4 (BRD4), was predicted by online algorithms and verified in human bronchial epithelial (HBE) cells. The expression of BRD4, interleukin (IL)-8, and IL-6 in the lung was also examined. The role of miR-29b in the inflammatory cytokine expression of airway epithelial cells was studied using an in vitro model system. In total, 60 subjects were recruited, including 10 nonsmokers, 24 smokers, and 26 patients with COPD. Both lung and plasma miR-29b are decreased in patients with COPD, and miR-29b expression levels are correlated with pulmonary function and inflammation. BRD4 is increased in the lung of patients with COPD and is correlated with miR-29b and IL-8 expression. miR-29b regulates cigarette smoke extract (CSE)-induced IL-8 expression by targeting BRD4 in HBE cells. The antioxidant N-acetylcysteine prevents CSE-induced miR-29b downregulation and BRD4 and IL-8 upregulation. Our findings indicate that miR-29b may participate in the airway inflammation in COPD by regulating inflammatory cytokine expression through targeting BRD4, plasma miR-29b may serve as a biomarker for disease severity in COPD, and oxidative stress may contribute to the decrease of miR-29b induced by cigarette smoke.
慢性阻塞性肺疾病（COPD）是一种常见的慢性气道炎症性疾病。研究表明，microRNAs 参与了炎症的调控。我们研究了 microRNA-29b（miR-29b）在 COPD 气道炎症中的作用。检测了肺和血浆中 miR-29b 的表达。利用在线算法预测 miR-29b 的靶标溴结构域蛋白 4（BRD4），并在人支气管上皮（HBE）细胞中进行验证。还检测了肺中 BRD4、白细胞介素（IL）-8 和 IL-6 的表达。利用体外模型系统研究了 miR-29b 对气道上皮细胞炎症细胞因子表达的作用。共招募了 60 名受试者，包括 10 名非吸烟者、24 名吸烟者和 26 名 COPD 患者。COPD 患者的肺和血浆 miR-29b 均降低，miR-29b 表达水平与肺功能和炎症相关。COPD 患者的肺中 BRD4 增加，与 miR-29b 和 IL-8 表达相关。miR-29b 通过靶向 BRD4 调节香烟烟雾提取物（CSE）诱导的 HBE 细胞中 IL-8 的表达。抗氧化剂 N-乙酰半胱氨酸可防止 CSE 诱导的 miR-29b 下调和 BRD4 和 IL-8 上调。我们的研究结果表明，miR-29b 可能通过靶向 BRD4 调节炎症细胞因子的表达参与 COPD 的气道炎症，血浆 miR-29b 可作为 COPD 疾病严重程度的生物标志物，氧化应激可能导致香烟烟雾引起的 miR-29b 减少。
