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LPS 刺激的正常人星形胶质细胞中 IL1RAP 的敲低抑制 LPS 诱导的反应性星形胶质细胞增生并促进神经元细胞增殖。

IL1RAP Knockdown in LPS-Stimulated Normal Human Astrocytes Suppresses LPS-Induced Reactive Astrogliosis and Promotes Neuronal Cell Proliferation.

机构信息

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.

出版信息

Neurochem Res. 2023 May;48(5):1468-1479. doi: 10.1007/s11064-022-03811-w. Epub 2022 Dec 11.

Abstract

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.

摘要

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。

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