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<p>Microglia-mediated neuroinflammation is closely associated with the pathogenesis of epilepsy. Mammalian sterile-20-like kinase 4 (MST4) has been suggested a regulator of inflammation. However, the effect of MST4 on microglia neuroinflammation in epilepsy remains unclear. A pilocarpine-induced rat epilepsy model was constructed and a lipopolysaccharide (LPS)-stimulated microglia cell model was applied in the current research. Knockdown or overexpression of MST4 was established using lentivirus transfection. Electroencephalograph (EEG) was employed to measure brain activities of rats. The protein and mRNA expressions were detected using western blot and qRT-PCR, respectively. Immunofluorescent staining was conducted to detect the distribution of the proteins. TUNEL staining was performed to evaluate cell apoptosis. The protein interaction was evaluated with Co-IP assay. Our results showed that MST4 and nuclear PKM2 expressions were increased in epileptic rats compared to control and colocalized with microglia. MST4 overexpression inhibited microglia activation, the release of TNF-α and IL-1β, and improved neuronal apoptosis in epileptic rats. Furthermore, MST4 interacted with PKM2 and regulated PKM2 nuclear translocation. Inhibiting PKM2 nuclear translocation by TEPP-46 reversed the promoting effect of MST4 knockdown on microglia neuroinflammation. In summary, our study demonstrated that MST4 alleviated microglia-mediated neuroinflammation in epilepsy, and the mechanism of MST4-mediated anti-neuroinflammatory effects may be associated with the inhibition of PKM2 nuclear translocation.</p>

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MST4 Regulates Microglia Neuroinflammation via Targeting PKM2 Nuclear Translocation in Epilepsy: An In Vivo and In Vitro Study

  • 期刊论文

  • 发表日期：

    2026年7月4日

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  • Jie Fu,
  • Shaotao Zhang,
  • Yifei Chu,
  • Jinglun Li,
  • Xiu Chen

摘要

Microglia-mediated neuroinflammation is closely associated with the pathogenesis of epilepsy. Mammalian sterile-20-like kinase 4 (MST4) has been suggested a regulator of inflammation. However, the effect of MST4 on microglia neuroinflammation in epilepsy remains unclear. A pilocarpine-induced rat epilepsy model was constructed and a lipopolysaccharide (LPS)-stimulated microglia cell model was applied in the current research. Knockdown or overexpression of MST4 was established using lentivirus transfection. Electroencephalograph (EEG) was employed to measure brain activities of rats. The protein and mRNA expressions were detected using western blot and qRT-PCR, respectively. Immunofluorescent staining was conducted to detect the distribution of the proteins. TUNEL staining was performed to evaluate cell apoptosis. The protein interaction was evaluated with Co-IP assay. Our results showed that MST4 and nuclear PKM2 expressions were increased in epileptic rats compared to control and colocalized with microglia. MST4 overexpression inhibited microglia activation, the release of TNF-α and IL-1β, and improved neuronal apoptosis in epileptic rats. Furthermore, MST4 interacted with PKM2 and regulated PKM2 nuclear translocation. Inhibiting PKM2 nuclear translocation by TEPP-46 reversed the promoting effect of MST4 knockdown on microglia neuroinflammation. In summary, our study demonstrated that MST4 alleviated microglia-mediated neuroinflammation in epilepsy, and the mechanism of MST4-mediated anti-neuroinflammatory effects may be associated with the inhibition of PKM2 nuclear translocation.