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miR-20b-5p exerts protective effects against experimental autoimmune encephalomyelitis in mice by inhibiting NLRP3 transcription and NLRP3/ASC/caspase-1 axis activation

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Abstract

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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Authors and Affiliations

  1. Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People’s Republic of China

    Fenggang Zhou

  2. Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, 150086, People’s Republic of China

    Fei Wu, Xinran Wang, Shihua Yu, Wenqi Tian & Ou Lv

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  1. Fenggang Zhou
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Contributions

FZ and FW: conceived and designed the experiments. FZ, XW, SY, WT, and OL: performed the experiments. FZ, XW, and WT: wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Ou Lv.

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Conflict of interest

Fenggang Zhou, Fei Wu, Xinran Wang, Shihua Yu, Wenqi Tian, and Ou Lv declares that has no conflict of interest.

Ethical approval

All animal experiments were conducted in compliance with the guidelines for experimental animal care and use (2011), and were approved by the Ethic Committee of The Second Affiliated Hospital of Harbin Medical University (SYDW2023-043). Adequate measures were taken to minimize animal suffering. All procedures were strictly implemented by the code of ethics.

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Zhou, F., Wu, F., Wang, X. et al. miR-20b-5p exerts protective effects against experimental autoimmune encephalomyelitis in mice by inhibiting NLRP3 transcription and NLRP3/ASC/caspase-1 axis activation. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00398-3

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