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Modulation of Microglia M2 Polarization and Alleviation of Hippocampal Neuron Injury By MiR-106b-5p/RGMa in a Mouse Model of Status Epilepticus

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Abstract

MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level. The miRNA miR-106b-5p has been linked to epilepsy, but its specific role and mechanism of action remain unclear. This was investigated in the present study using a mouse model of pilocarpine-induced status epilepticus and an in vitro system of HT22 hippocampal cells treated with Mg2+-free solution and cocultured with BV2 microglia cells. We found that inhibiting miR-106b-5p expression promoted microglia M2 polarization, reduced the inflammatory response, and alleviated neuronal injury. These effects involved modulation of the repulsive guidance molecule A (RGMa)–Rac1–c-Jun N-terminal kinase (JNK)/p38–mitogen-activated protein kinase (MAPK) signaling axis. Our results suggest that therapeutic strategies targeting miR-106b-5p or downstream factors can be effective in preventing epileptogenesis or treating epilepsy.

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DATA AVAILABILITY

All data generated or analyzed in this study are included in this article. The datasets used and/or analyzed in the study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from CAAE Epilepsy Research Fund (CX-B-2021–02).

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  1. Department of Pediatrics, Shengjing Hospital of China Medical University, Liaoning Province, Shenyang City, 110004, China

    Tao Yu, Liang Huo, Jie Lei, Jing‑Jing Sun & Hua Wang

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All authors contributed to study conception and design. The first draft of the manuscript was written by Tao Yu, and all authors commented on previous versions of the manuscript and read and approved the final manuscript.

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Correspondence to Hua Wang.

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Animal experiments were approved by the Animal Ethics Committee of Shengjing Hospital Affiliated with China Medical University (no. 2020PS505K).

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Yu, T., Huo, L., Lei, J. et al. Modulation of Microglia M2 Polarization and Alleviation of Hippocampal Neuron Injury By MiR-106b-5p/RGMa in a Mouse Model of Status Epilepticus. Inflammation 45, 2223–2242 (2022). https://doi.org/10.1007/s10753-022-01686-1

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