MiR-122-5p protects against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells
MiR-122-5p protects against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells
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MiR-122-5p 通过调节肺微血管内皮细胞中的 DUSP4/ERK 信号传导来预防急性肺损伤
DOI：
10.1016/j.lfs.2020.117851
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发表时间：
2020-09-01
期刊：
影响因子：
6.1
通讯作者：
Geng, Qing
中科院分区：
文献类型：
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作者：
Lu, Zilong;Feng, Haojie;Geng, Qing
目的：本研究旨在探讨miR-122-5p在急性肺损伤中的作用。材料与方法：采用小鼠气管内注射脂多糖建立急性肺损伤模型。小鼠还通过注射给予miR-122-5p拮抗剂和mimic，分别抑制或过表达miR-122-5p在肺组织中。在体外实验中，我们分离了原代小鼠肺微血管内皮细胞，并通过脂多糖处理建立了细胞损伤模型。主要发现：注射miR-122-5p拮抗剂的小鼠表现出减轻的肺损伤、炎症和氧化应激，而注射miR-122-5p模拟物的小鼠表现出加重的肺损伤、炎症和氧化应激。在体外实验中，我们发现miR-122-5p拮抗剂抑制脂多糖诱导的炎症、细胞凋亡和氧化应激。此外，miR-122-5p调节DUSP4的启动子活性，从而负向调节ERK1/2信号通路。DUSP4 siRNA的使用抵消了miR-122-5p拮抗剂的作用。意义：综上所述，这些结果表明miR-122-5p通过调节肺微血管内皮细胞中的DUSP4/ERK信号传导来保护急性肺损伤。MiR-122-5p拮抗剂可能是一种很有前景的治疗急性肺损伤的方法。
Aims: The aim of this study was to explore the role of miR-122-5p in acute lung injury.Materials and methods: Mice were subjected to intratracheal injection of lipopolysaccharide to establish an acute lung injury model. The mice also received miR-122-5p antagonist and mimic via injection to inhibit or over-express miR-122-5p in the lung tissue, respectively. In an in vitro experiment, we isolated primary mouse lung microvascular endothelial cells and established a cell injury model via lipopolysaccharide treatment.Key findings: Mice injected with an miR-122-5p antagonist exhibited reduced lung injury, inflammation and oxidative stress, while mice injected with a miR-122-5p mimic exhibited exaggerated lung injury, inflammation and oxidative stress. In an in vitro experiment, we found that the miR-122-5p antagonist suppressed lipopolysaccharide-induced inflammation, apoptosis and oxidative stress. Moreover, miR-122-5p regulated the promoter activity of DUSP4, which negatively regulated ERK1/2 signaling. The use of DUSP4 siRNA counteracted the effects of the miR-122-5p antagonist.Significance: Taken together, these results show that miR-122-5p protected against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells. MiR-122-5p antagonism may be a promising treatment method for acute lung injury.