Spinal cord injury (SCI) is a significant contributor to disability in contemporary society, resulting in substantial psychological and economic burdens for patients and their family. Microglia-mediated inflammation is an important factor affecting the nerve repair of SCI patients. N⁶-methyladenosine (m⁶A) is a prevalent epigenetic modification in mammals, which shows a strong association with inflammation. However, the mechanism of m⁶A modification regulating microglia-mediated inflammation is still unclear. Here, we observed that METTL3, a m⁶A methylase, was increased in SCI mice and lipopolysaccharide (LPS)-exposed BV2 cells. Knockdown of METTL3 inhibited the increased expression of iNOS and IL-1β induced by LPS in vitro. Subsequently, MEF2C, myocyte-specific enhancer factor 2C, was decreased in SCI mice and LPS-exposed BV2 cells. Knockdown of MEF2C promoted the expression of iNOS and IL-1β. Sequence analysis showed that there were multiple highly confident m⁶A modification sites on the MEF2C mRNA. METTL3 antibody could pull down a higher level of MEF2C mRNA than the IgG in RNA binding protein immunoprecipitation assay. Knockdown of METTL3 promoted MEF2C protein expression and MEF2C mRNA expression, accompanied by a reduced m⁶A modification level on the MEF2C mRNA. Knockdown of MEF2C inhibited the anti-inflammatory effect of METTL3 siRNA. Our results suggest that METTL3 promotes microglia inflammation via regulating MEF2C mRNA m⁶A modification induced by SCI and LPS treatment.

脊髓损伤（SCI）是当代社会残疾的一个重要原因，给患者及其家人带来沉重的心理和经济负担。小胶质细胞介导的炎症是影响SCI患者神经修复的重要因素。N ⁶ -甲基腺苷 (m ⁶ A) 是哺乳动物中普遍存在的表观遗传修饰，与炎症密切相关。^{然而，m 6} A 修饰调节小胶质细胞介导的炎症的机制仍不清楚。在这里，我们观察到 METTL3（am ⁶ A 甲基化酶）在 SCI 小鼠和暴露于脂多糖 (LPS) 的 BV2 细胞中增加。METTL3 的敲低抑制了 LPS 体外诱导的 iNOS 和 IL-1β 表达的增加。随后，在 SCI 小鼠和暴露于 LPS 的 BV2 细胞中，MEF2C（肌细胞特异性增强因子 2C）下降。MEF2C 的敲低促进了 iNOS 和 IL-1β 的表达。序列分析显示MEF2C mRNA上存在多个高度可信的m ^{6 A修饰位点。}在 RNA 结合蛋白免疫沉淀测定中，METTL3 抗体比 IgG 能够降低更高水平的 MEF2C mRNA。METTL3的敲低促进了MEF2C蛋白表达和MEF2C mRNA表达，同时MEF2C mRNA上的m ^{6 A修饰水平降低。}MEF2C 的敲低抑制了 METTL3 siRNA 的抗炎作用。我们的结果表明，METTL3 通过调节 SCI 和 LPS 治疗诱导的 MEF2C mRNA m ⁶ A 修饰来促进小胶质细胞炎症。