Zhang Bo, Zhang Qing, Yang Linying, Zheng Hongfei, Pang Guifen, Zhao Mingzhen, Sun Bo, Cao Jie
Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei, China.
Evid Based Complement Alternat Med. 2022 Apr 11;2022:2408682. doi: 10.1155/2022/2408682. eCollection 2022.
Acute lung injury (ALI)/acute respiratory distress syndrome is a common clinical syndrome characterized by respiratory failure. MicroRNAs (miRNAs) are closely related to ALI and acute respiratory distress syndrome. TargetScan software analysis showed that miR-584-5p can bind to the 3' noncoding region of , which is involved in the occurrence and development of ALI, thereby affecting the inflammatory pathway and inflammation development. Thus, we aimed to determine whether miR-584-5p affects ALI. Human bronchial epithelial (16-HBE) cells were transfected with miR-584-5p mimics or inhibitors and then stimulated with lipopolysaccharide (LPS).The cell viability, apoptosis, release of proinflammatory factors, mTOR, and NF-B pathway protein expression were evaluated respectively. Mimic584 increased, whereas inhibitor584 decreased, LPS-stimulated inflammation. The protein expression of inflammatory factors was significantly increased in 16-HBE cells in the mimic584 + LPS group and decreased in the inhibitor584 + LPS group. Mimic584 activated mTOR and the NF-B-related proteins P65 and p-p65, whereas inhibitor584 inactivated the proteins in 16-HBE cells. Overexpression of miR-584 significantly promoted apoptosis in LPS-stimulated 16-HBE cells. There were no differences in the proliferation and cell cycle of LPS-stimulated 16-HBE cells regardless of mimic584 or inhibitor584 transfection. Collectively, we demonstrated that inhibitor584 can alleviate ALI-induced expression of inflammatory factors via mTOR signaling and the NF-B pathway. In conclusion, we found that inhibitor584 transfection could be a potential therapeutic strategy for ALI.
急性肺损伤（ALI）/急性呼吸窘迫综合征是一种以呼吸衰竭为特征的常见临床综合征。微小RNA（miRNA）与ALI和急性呼吸窘迫综合征密切相关。TargetScan软件分析表明，miR-584-5p可与参与ALI发生发展的[某基因]的3'非编码区结合，从而影响炎症通路和炎症发展。因此，我们旨在确定miR-584-5p是否影响ALI。将人支气管上皮（16-HBE）细胞用miR-584-5p模拟物或抑制剂转染，然后用脂多糖（LPS）刺激。分别评估细胞活力、凋亡、促炎因子释放、mTOR和NF-κB通路蛋白表达。Mimic584增加而inhibitor584降低LPS刺激的炎症反应。在mimic584 + LPS组的16-HBE细胞中炎症因子的蛋白表达显著增加，而在inhibitor584 + LPS组中降低。Mimic584激活mTOR以及与NF-κB相关的蛋白P65和p-p65，而inhibitor584使16-HBE细胞中的这些蛋白失活。miR-584的过表达显著促进LPS刺激的16-HBE细胞凋亡。无论转染mimic584还是inhibitor584，LPS刺激的16-HBE细胞的增殖和细胞周期均无差异。总体而言，我们证明inhibitor584可通过mTOR信号传导和NF-κB通路减轻ALI诱导的炎症因子表达。总之，我们发现转染inhibitor584可能是ALI的一种潜在治疗策略。
