Cell Biology Department, Wuxi School of Medicine, Jiangnan University, 214122 Wuxi, Jiangsu, China.
Department of Pathogen Biology, Guizhou Nursing Vocational College, 550081 Guiyang, Guizhou, China.
J Integr Neurosci. 2023 Jul 13;22(4):96. doi: 10.31083/j.jin2204096.
Few studies have reported the direct effect of C-X-C motif chemokine ligand 10 (CXCL10) and Neuregulin 1 (Nrg1) on neurons after spinal cord injury (SCI). This study reports the role of CXCL10 in the regulation of neuronal damage after SCI and the potential therapeutic effect of Nrg1.
The expression level of and in SCI mice was analyzed in the Gene Expression Omnibus DataSets, followed by immunohistochemical confirmation using a mouse SCI model. HT22 cells and NSC34 cells were treated with CXCL10 and Nrg1, individually or in combination, and then assayed for cell viability. The percentage of wound closure was determined through the cell scratch injury model using HT22 and NSC34 cells. Potential molecular mechanisms were also tested in response to either the individual administration of CXCL10 and Nrg1 or a mixture of both molecules.
C expression was significantly increased in both young and old mice subjected to SCI, while expression was significantly decreased. CXCL10 induced a decrease in cell viability, which was partially reversed by Nrg1. CXCL10 failed to inhibit scratch healing in HT22 and NSC34 cells, while Nrg1 promoted scratch healing. At the molecular level, CXCL10-activated cleaved caspase 9 and cleaved caspase 3 were both inhibited by Nrg1 through pERK1/2 signaling in HT22 and NSC34 cells.
CXCL10 is upregulated in SCI. Despite the negative effect on cell viability, CXCL10 failed to inhibit the scratch healing of HT22 and NSC34 cells. Nrg1 may protect neurons by partially antagonizing the effect of CXCL10.
鲜有研究报道过 C-X-C 基元趋化因子配体 10（CXCL10）和神经调节蛋白 1（Nrg1）对脊髓损伤（SCI）后神经元的直接作用。本研究报告了 CXCL10 在 SCI 后神经元损伤调节中的作用以及 Nrg1 的潜在治疗效果。
在基因表达综合数据库数据集（Gene Expression Omnibus DataSets）中分析 SCI 小鼠中 和 的表达水平，然后使用小鼠 SCI 模型进行免疫组织化学验证。单独或联合使用 CXCL10 和 Nrg1 处理 HT22 细胞和 NSC34 细胞，并检测细胞活力。通过 HT22 和 NSC34 细胞的细胞划痕损伤模型确定伤口闭合的百分比。还针对单独给予 CXCL10 和 Nrg1 或两者混合物的反应测试了潜在的分子机制。
在 SCI 后的年轻和老年小鼠中，表达显著增加，而表达显著降低。CXCL10 诱导细胞活力下降，而 Nrg1 部分逆转了这一作用。CXCL10 未能抑制 HT22 和 NSC34 细胞的划痕愈合，而 Nrg1 则促进了划痕愈合。在分子水平上，CXCL10 激活的裂解 caspase 9 和裂解 caspase 3 均通过 HT22 和 NSC34 细胞中的 pERK1/2 信号被 Nrg1 抑制。
CXCL10 在 SCI 中上调。尽管对细胞活力有负面影响，但 CXCL10 未能抑制 HT22 和 NSC34 细胞的划痕愈合。Nrg1 可能通过部分拮抗 CXCL10 的作用来保护神经元。
