Neonatal Medical Center, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu Province, China.
Department of Pediatrics, The Central Hospital of Enshi Autonomous Prefecture, Enshi City 445000, Hubei Province, China.
Biomed Pharmacother. 2019 Apr;112:108664. doi: 10.1016/j.biopha.2019.108664. Epub 2019 Feb 20.
Acute lung injury (ALI) is the leading cause of human death, and it is widely accepted that the runaway inflammation is an important risk for the development of ALI. In the present study, we aimed to investigate the effect of miR-16 on lipopolysaccharide-induced acute lung injury in mice, especially focusing on Toll-like receptor 4 (TLR4) and NF-kB signaling pathway as well as NOD-like receptor protein 3 (NLRP3) inflammasome activation. We established in vivo and in vitro model of ALI using LPS and demonstrated that miR-16 expression was down-regulated in lung tissue as well as A549 cells after 8 h of LPS treatment. Furthermore, when miR-16 levels in lung tissues were up-regulated by miR-16 agomir, it was confirmed that the mRNA and protein levels of NF-κB, NLRP3 inflammasome, and inflammatory factors were decreased by the miR-16 by directly targeting TLR4. We also treated A549 cells with miR-16 mimics and anti-miR-16 to confirm the results. Overall, our experiments showed that miR-16 protects against acute lung injury in mice by regulating the TLR4/ NF-κB pathway and attenuating inflammatory response. This work suggests a potential novel therapeutic approach to combat ALI.
急性肺损伤（ALI）是人类死亡的主要原因，广泛认为失控的炎症是 ALI 发展的重要风险因素。在本研究中，我们旨在研究 miR-16 对脂多糖诱导的小鼠急性肺损伤的影响，特别是关注 Toll 样受体 4（TLR4）和 NF-κB 信号通路以及 NOD 样受体蛋白 3（NLRP3）炎症小体的激活。我们使用 LPS 建立了体内和体外的 ALI 模型，并证明 LPS 处理 8 小时后，肺组织和 A549 细胞中的 miR-16 表达下调。此外，当 miR-16 在肺组织中的水平通过 miR-16 agomir 上调时，通过直接靶向 TLR4，证实 NF-κB、NLRP3 炎症小体和炎症因子的 mRNA 和蛋白水平降低。我们还使用 miR-16 模拟物和抗 miR-16 处理 A549 细胞以确认结果。总的来说，我们的实验表明，miR-16 通过调节 TLR4/NF-κB 通路和减轻炎症反应来保护小鼠免受急性肺损伤。这项工作为对抗 ALI 提供了一种潜在的新的治疗方法。
