Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Brain Pathol. 2022 Sep;32(5):e13070. doi: 10.1111/bpa.13070. Epub 2022 Mar 25.
The M1 polarization of microglia and neuroinflammation restrict the treatment of acute spinal cord injury (ASCI), and long non-coding ribonucleic acid (lncRNA) maternally expressed gene 3 (MEG3) expression is lessened in ASCI. However, the function and mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI are unclear. The expressions of lncRNA MEG3 in ASCI mouse spinal cord tissues and lipopolysaccharide (LPS)-treated primary microglia and BV2 cells were quantified through a quantitative real-time polymerase chain reaction. In-vitro assays were conducted to explore the function of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. RNA degradation, RNA immunoprecipitation, RNA pull-down, cycloheximide-chase, and ubiquitination analyses were carried out to probe into the mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. The lncRNA MEG3 expression was lessened in the ASCI mouse spinal cord tissues and LPS-treated primary microglia and BV2 cells, and the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia and the neuroinflammation by regulating the NF-κB signaling pathway. For the investigation of the potential mechanism of such, the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF-κB axis and boosted the motor function recovery and neuroinflammation relief in the mice with SCI. The overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF-κB axis.
小胶质细胞 M1 极化和神经炎症限制了急性脊髓损伤 (ASCI) 的治疗，并且 ASCI 中长链非编码核糖核酸 (lncRNA) 母系表达基因 3 (MEG3) 的表达减少。然而，lncRNA MEG3 在 ASCI 中小胶质细胞 M1 极化和神经炎症中的功能和机制尚不清楚。通过实时定量聚合酶链反应定量检测 ASCI 小鼠脊髓组织和脂多糖 (LPS) 处理的原代小胶质细胞和 BV2 细胞中 lncRNA MEG3 的表达。进行体外测定以研究 lncRNA MEG3 在 ASCI 中小胶质细胞 M1 极化和神经炎症中的功能。进行 RNA 降解、RNA 免疫沉淀、RNA 下拉、环己酰亚胺追踪和泛素化分析以探究 lncRNA MEG3 在 ASCI 中小胶质细胞 M1 极化和神经炎症中的机制。lncRNA MEG3 在 ASCI 小鼠脊髓组织和 LPS 处理的原代小胶质细胞和 BV2 细胞中的表达减少，lncRNA MEG3 的过表达通过调节 NF-κB 信号通路抑制小胶质细胞 M1 极化和神经炎症。为了研究这种潜在机制，lncRNA MEG3 的过表达通过 HuR/A20/NF-κB 轴抑制小胶质细胞 M1 极化，并促进 SCI 小鼠运动功能恢复和神经炎症缓解。lncRNA MEG3 通过 HuR/A20/NF-κB 轴抑制小胶质细胞 M1 极化。
