Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Department of Orthopedics, The First Hospital of Changsha City, Changsha, 410005, China.
Neurochem Res. 2023 May;48(5):1468-1479. doi: 10.1007/s11064-022-03811-w. Epub 2022 Dec 11.
The reactivation of astrocytes plays a critical role in spinal cord injury (SCI) repairment. In this study, IL1RAP expression has been found to be upregulated in SCI mice spinal cord, SCI astrocytes, and LPS-stimulated NHAs. Genes correlated with IL1RAP were significantly enriched in cell proliferation relative pathways. In LPS-stimulated NHAs, IL1RAP overexpression promoted NHA cell proliferation, decreased PTEN protein levels, and increased the phosphorylation of Akt and mTOR. IL1RAP overexpression promoted LPS-induced NHA activation and NF-κB signaling activation. Conditioned medium from IL1RAP-overexpressing NHAs inhibited SH-SY5Y cells viability but promoted cell apoptosis. Conclusively, IL1RAP knockdown in LPS-stimulated NHAs could partially suppress LPS-induced reactive astrogliosis, therefore promoting neuronal cell proliferation.
星形胶质细胞的再激活在脊髓损伤 (SCI) 修复中起着关键作用。在这项研究中,发现白细胞介素 1 受体相关蛋白 (IL1RAP) 在 SCI 小鼠脊髓、SCI 星形胶质细胞和脂多糖 (LPS) 刺激的 NHAs 中表达上调。与 IL1RAP 相关的基因在细胞增殖相关途径中显著富集。在 LPS 刺激的 NHAs 中,IL1RAP 过表达促进 NHAs 细胞增殖,降低 PTEN 蛋白水平,并增加 Akt 和 mTOR 的磷酸化。IL1RAP 过表达促进 LPS 诱导的 NHAs 激活和 NF-κB 信号激活。来自过表达 IL1RAP 的 NHAs 的条件培养基抑制 SH-SY5Y 细胞活力,但促进细胞凋亡。结论是,在 LPS 刺激的 NHAs 中敲低 IL1RAP 可以部分抑制 LPS 诱导的反应性星形胶质细胞增生,从而促进神经元细胞增殖。