miR-124-3p 通过靶向 PDE4B 减轻 LPS 诱导的 ALI 通过 TLR4/NF-κB 信号通路。
MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4/NF-κB signaling pathway.
机构信息
Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Pathology Laboratory of Sichuan University, Chengdu, Sichuan, China.
出版信息
Int Immunopharmacol. 2022 Apr;105:108540. doi: 10.1016/j.intimp.2022.108540. Epub 2022 Jan 18.
BACKGROUND
A large number of studies have found that microRNAs (miRNAs) and phosphodiesterase 4 (PDE4) are crucial regulators of inflammatory responses in acute lung injury (ALI).
OBJECTIVE
This study will explore the protective effect of miR-124-3p on ALI and its related mechanism.
METHODS
The ALI mouse model was established by intratracheal administration of lipopolysaccharide (LPS) and evaluated by haematoxylin and eosin (HE) staining, lung injury score, inflammation factors, polymorphonuclear leukocyte (PMN) count, total protein and lung wet weight/dry weight (W/D) ratio. MiR-124-3p was overexpressed in vivo by intratracheal administration of miR-agomir, and PDE4B was expressed at low level in vivo by intratracheal administration of a PDE4B inhibitor. The mRNA expression level was detected by qRT-PCR, and the protein expression level was detected by Western blot. The relationship between miR-124-3p and PDE4B was detected by dual-luciferase activity assay.
RESULTS
We found that miR-124-3p was downregulated in LPS-induced ALI. Overexpression of miR-124-3p alleviated lung injury by inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, we confirmed that miR-124-3p suppressed the TLR4/NF-κB signaling pathway by directly targeting PDE4B.
CONCLUSION
miR-124-3p targeting PDE4B had a protective effect on LPS-induced ALI by inhibiting the TLR4/NF-κB signaling pathway.
背景
大量研究发现 microRNAs（miRNAs）和磷酸二酯酶 4（PDE4）是急性肺损伤（ALI）中炎症反应的关键调节因子。
目的
本研究旨在探讨 miR-124-3p 对 ALI 的保护作用及其相关机制。
方法
通过气管内给予脂多糖（LPS）建立 ALI 小鼠模型，通过苏木精-伊红（HE）染色、肺损伤评分、炎症因子、多形核白细胞（PMN）计数、总蛋白和肺湿重/干重（W/D）比进行评估。通过气管内给予 miR-agomir 体内过表达 miR-124-3p，通过气管内给予 PDE4B 抑制剂体内低表达 PDE4B。通过 qRT-PCR 检测 mRNA 表达水平，通过 Western blot 检测蛋白表达水平。通过双荧光素酶活性测定检测 miR-124-3p 与 PDE4B 之间的关系。
结果
我们发现 LPS 诱导的 ALI 中 miR-124-3p 下调。过表达 miR-124-3p 通过抑制 Toll 样受体 4（TLR4）/核因子-κB（NF-κB）信号通路缓解肺损伤。此外，我们证实 miR-124-3p 通过直接靶向 PDE4B 抑制 TLR4/NF-κB 信号通路。
结论
miR-124-3p 通过靶向 PDE4B 抑制 TLR4/NF-κB 信号通路对 LPS 诱导的 ALI 具有保护作用。
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