Fu Qiang, Zou Ming-Ming, Zhu Jian-Wei, Zhang Yan, Chen Wen-Jin, Cheng Mei, Liu Chun-Feng, Ma Quan-Hong, Xu Ru-Xiang
Affiliated Bayi Brain Hospital, P.L.A. Army General Hospital, Beijing 100700, China.
Department of Neurosurgery, The 251st Hospital of P.L.A., Zhangjiakou 075000, China.
Oncotarget. 2017 Jul 11;8(28):45380-45390. doi: 10.18632/oncotarget.17492.
Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit the axonal regeneration after spinal cord injury (SCI). However, the underlying molecular mechanisms remain unclear. In the present study, we identify tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in glial cells in the normal uninjured spinal cord, exhibits strong expression in both astrocytes and microglia following SCI. We further observe that deficiency of TRIM32 results in increased numbers of astrocytes and microglia, which is accompanied by enhanced proliferation of both cells and increased secretion of interleukin (IL)-1 and IL-10. The axonal regeneration is impaired in the spinal cord of TRIM32-/- mice following SCI, which is indicated by increased distances of the corticospinal tracts (CST) fiber to the lesion site and less axonal sprouting. We further show that deficiency of TRIM32 results in delay motor recovery following SCI. Therefore, TRIM32 is a novel essential positive factor modulating axonal regeneration and the recovery of motor function following SCI, possibly through suppressing proliferation of glial cells.
外在环境因素和内在神经元机制均会限制脊髓损伤（SCI）后的轴突再生。然而，其潜在分子机制仍不清楚。在本研究中，我们鉴定出三联基序蛋白32（TRIM32），一种E3泛素连接酶，在正常未损伤脊髓的胶质细胞中几乎检测不到，但在SCI后星形胶质细胞和小胶质细胞中均表现出强表达。我们进一步观察到，TRIM32缺陷导致星形胶质细胞和小胶质细胞数量增加，同时伴随着这两种细胞增殖增强以及白细胞介素（IL）-1和IL-10分泌增加。SCI后，TRIM32基因敲除小鼠脊髓中的轴突再生受损，这表现为皮质脊髓束（CST）纤维到损伤部位的距离增加以及轴突发芽减少。我们进一步表明，TRIM32缺陷导致SCI后运动恢复延迟。因此，TRIM32是一种新型的重要正向因子，可能通过抑制胶质细胞增殖来调节SCI后的轴突再生和运动功能恢复。
