eIF5A1/RhoGDIα pathway: a novel therapeutic target for treatment of spinal cord injury identified by a proteomics approach.
eIF5A1/RhoGDIα pathway: a novel therapeutic target for treatment of spinal cord injury identified by a proteomics approach.
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DOI：
10.1038/srep16911
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发表时间：
2015-11-23
影响因子：
4.6
通讯作者：
Wang TH
中科院分区：
文献类型：
--
作者：
Liu W;Shang FF;Xu Y;Belegu V;Xia L;Zhao W;Liu R;Wang W;Liu J;Li CY;Wang TH
脊髓损伤（SCI）通常伴随着一定程度的自发性功能恢复。产生这种复苏的基本机制仍然难以捉摸。在这项研究中，我们观察到一个显着的自发运动功能恢复后14至28天脊髓横断（SCT）大鼠。使用比较蛋白质组学的方法，尾部的损伤，我们检测到20个蛋白质的差异。其中两种蛋白是真核生物翻译起始因子5A 1（eIF 5A 1），其参与细胞存活和增殖，以及Rho GDP解离抑制剂α（RhoGDIα），其是Rho GDI家族的成员，其参与细胞骨架重组。在确认SCT后这两种蛋白质表达水平的变化后，我们发现体内eIF 5A 1上调和下调分别显著增加和减少运动功能恢复。在体外，eIF 5A 1在原代神经元中的过表达增加了细胞存活和延长了神经突长度，而eIF 5A 1敲低逆转了这些结果。我们发现RhoGDIα的上调和下调挽救了eIF 5A 1在体内和体外的下调和上调效应。因此，我们将eIF 5A 1/RhoGDIα通路作为治疗脊髓损伤的新靶点。
Spinal cord injury (SCI) is frequently accompanied by a degree of spontaneous functional recovery. The underlying mechanisms through which such recovery is generated remain elusive. In this study, we observed a significant spontaneous motor function recovery 14 to 28 days after spinal cord transection (SCT) in rats. Using a comparative proteomics approach, caudal to the injury, we detected difference in 20 proteins. Two of these proteins, are eukaryotic translation initiation factor 5A1 (eIF5A1) that is involved in cell survival and proliferation, and Rho GDP dissociation inhibitor alpha (RhoGDIα), a member of Rho GDI family that is involved in cytoskeletal reorganization. After confirming the changes in expression levels of these two proteins following SCT, we showed that in vivo eIF5A1 up-regulation and down-regulation significantly increased and decreased, respectively, motor function recovery. In vitro, eIF5A1 overexpression in primary neurons increased cell survival and elongated neurite length while eIF5A1 knockdown reversed these results. We found that RhoGDIα up-regulation and down-regulation rescues the effect of eIF5A1 down-regulation and up-regulation both in vivo and in vitro. Therefore, we have identified eIF5A1/RhoGDIα pathway as a new therapeutic target for treatment of spinal cord injured patients.