Background

Experimental autoimmune encephalomyelitis (EAE) is a fatal autoimmune disease, and microRNAs (miRNAs) play vital roles in regulating immune responses.

Objectives

This study aimed to explore the effect of miR-20b-5p in mice with EAE as well as the underlying mechanism.

Methods

An EAE mouse model was established via myelin oligodendrocyte glycoprotein (MOG)35–55 peptide induction, and miR-20b-5p expression was measured. Then, miR-20b-5p agomiR was injected via the caudal vein. Clinical score evaluation, body weight measurement, and histological staining were performed, and lactic dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT) and reactive oxygen species (ROS) levels were measured. The binding of miR-20b-5p to Nod-like receptor protein 3 (NLRP3) was analysed by dual-luciferase assay. Levels of NLRP3, ASC and caspase-1 were measured. The effect of NLRP3 on EAE model mice was analysed via rescue experiments.

Results

The clinical scores and body weight of EAE model mice were reduced, and tissue damage was exacerbated. miR-20b-5p was expressed at low levels in EAE model mice, and their symptoms were ameliorated after miR-20b-5p overexpression. Moreover, miR-20b-5p overexpression alleviated pyroptosis, inflammation and oxidative stress in the spinal cord tissues of EAE model mice. Mechanistically, miR-20b-5p targeted NLRP3 transcription and inhibited NLRP3/ASC/caspase-1 pathway activation. NLRP3 overexpression activated the NLRP3/ASC/caspase-1 pathway and abolished the protective effect of miR-20b-5p on EAE.

Conclusion

miR-20b-5p exerted a protective effect on EAE in mice by inhibiting NLRP3 transcription and NLRP3/ASC/caspase-1 pathway activation.

中文翻译：

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miR-20b-5p通过抑制NLRP3转录和NLRP3/ASC/caspase-1轴激活对小鼠实验性自身免疫性脑脊髓炎发挥保护作用

背景

实验性自身免疫性脑脊髓炎（EAE）是一种致命的自身免疫性疾病，microRNA（miRNA）在调节免疫反应中发挥着至关重要的作用。

目标

本研究旨在探讨miR-20b-5p对EAE小鼠的影响及其潜在机制。

方法

通过髓鞘少突胶质细胞糖蛋白 (MOG)35-55 肽诱导建立 EAE 小鼠模型，并测量 miR-20b-5p 表达。然后，通过尾静脉注射miR-20b-5p agomiR。进行临床评分评估、体重测量和组织学染色，并测量乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和活性氧（ROS）水平。通过双荧光素酶测定分析 miR-20b-5p 与 Nod 样受体蛋白 3 (NLRP3) 的结合。测量 NLRP3、ASC 和 caspase-1 的水平。通过拯救实验分析NLRP3对EAE模型小鼠的影响。

结果

EAE模型小鼠临床评分和体重降低，组织损伤加剧。miR-20b-5p在EAE模型小鼠中低水平表达，miR-20b-5p过表达后症状得到改善。此外，miR-20b-5p过表达可减轻EAE模型小鼠脊髓组织中的细胞焦亡、炎症和氧化应激。从机制上讲，miR-20b-5p 靶向 NLRP3 转录并抑制 NLRP3/ASC/caspase-1 通路激活。NLRP3过表达激活NLRP3/ASC/caspase-1通路并消除miR-20b-5p对EAE的保护作用。

结论

miR-20b-5p通过抑制NLRP3转录和NLRP3/ASC/caspase-1通路激活对小鼠EAE发挥保护作用。