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A Causal Relationship in Spinal Cord Injury Rat Model Between Microglia Activation and EGFR/MAPK Detected by Overexpression of MicroRNA-325-3p

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Abstract

Microglial activation and inflammatory response played an important role in the secondary injury of spinal cord injury (SCI). Several microRNAs were associated with this procedure, but the underlying molecular mechanism was poorly understood. Sprague-Dawley (SD) rats were divided into four groups: SCI group (n = 7), agomiR-325-3p group (n = 7), and their control groups. Expression of miR-325-3p and proteins in epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway was evaluated in microglia from SCI rats and primary microglia/BV2 cells activated by lipopolysaccharide (LPS). Concentrations of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in supernatants were measured by ELISA. Low expression of miR-325-3p and activation of EGFR/MAPK was observed in microglia of SCI and LPS-induced primary microglia. Overexpression of miR-325-3p in LPS-induced BV2 cells inhibited microglial activation and release of TNF-α and IL-1β. Luciferase reporter assay confirmed that miR-325-3p negatively regulated EGFR by targeting its 3′-untranslated regions. Additionally, agomiR-325-3p inhibited the activation of microglia and EGFR/MAPK, alleviating the inflammatory response. These results indicated that miR-325-3p attenuated secondary injury after SCI through inhibition of EGFR/MAPK signaling pathway, the microglial activation, and the release of inflammatory cytokines, suggesting that miR-325-3p may be employed as a therapeutic target for SCI.

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Availability of Data and Material

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

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Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Erqi District, Zhengzhou, 450003, Henan Province, China

    Penghui Yan, Xuejian Wu, Xiaokang Liu, Yingchun Cai, Chenglong Shao & Guangduo Zhu

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  1. Penghui Yan
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  2. Xuejian Wu
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  3. Xiaokang Liu
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  4. Yingchun Cai
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  5. Chenglong Shao
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  6. Guangduo Zhu
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Correspondence to Xuejian Wu.

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All experimental procedures were performed in accordance with protocols approved by the Governmental Animal Care Committee of the First Affiliated Hospital of Zhengzhou University.

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Yan, P., Wu, X., Liu, X. et al. A Causal Relationship in Spinal Cord Injury Rat Model Between Microglia Activation and EGFR/MAPK Detected by Overexpression of MicroRNA-325-3p. J Mol Neurosci 68, 181–190 (2019). https://doi.org/10.1007/s12031-019-01297-w

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  • DOI: https://doi.org/10.1007/s12031-019-01297-w

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