MiR-20a Plays a Key Regulatory Role in the Repair of Spinal Cord Dorsal Column Lesion via PDZ-RhoGEF/RhoA/GAP43 Axis in Rat
MiR-20a Plays a Key Regulatory Role in the Repair of Spinal Cord Dorsal Column Lesion via PDZ-RhoGEF/RhoA/GAP43 Axis in Rat
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DOI：
10.1007/s10571-018-0635-0
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发表时间：
2018-11
影响因子：
4
通讯作者：
Tianyi Wang;Bo Li;Xin Yuan;L. Cui;Zhijie Wang;Yanjun Zhang;Mei Yu;Yucai Xiu;Zheng Zhang-Zheng-Zh
中科院分区：
文献类型：
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作者：
Tianyi Wang;Bo Li;Xin Yuan;L. Cui;Zhijie Wang;Yanjun Zhang;Mei Yu;Yucai Xiu;Zheng Zhang-Zheng-Zh
脊髓损伤（SCI）可引起感觉异常、感觉不良和慢性神经性疼痛等感觉功能障碍。MiR-20a促进皮层神经元的轴突生长。然而，miR-20a在初级感觉神经元轴突生长和脊髓背柱病变（SDCL）中的作用尚不清楚。因此，我们研究了miR-20a在大鼠sdcl后的作用。体外应用NF-200免疫荧光染色观察miR-20a或PDZ-RhoGEF对DRG神经元轴突生长的影响。RT-PCR定量检测miR-20a的表达。Western blotting分析miR-20a或PDZ-RhoGEF被调节后PDZ-RhoGEF/RhoA/GAP43轴的表达。采用体感诱发电位和去带试验评价脊髓感觉传导功能。结果显示，sdcl后miR-20a的表达呈时间依赖性下降。在体外，miR-20a调控轴突生长和PDZ-RhoGEF/RhoA/GAP43轴的表达。体内调节miR-20a可改变miR-20a- pdz - rhogef /RhoA/GAP43轴的表达，促进sdcl后上升感觉功能的恢复。结果提示miR-20a/PDZ-RhoGEF/RhoA/GAP43轴与SDCL的病理生理过程相关。因此，靶向miR-20a/PDZ-RhoGEF /RhoA/GAP43轴是促进脊髓损伤后感觉功能恢复的新策略。
Spinal cord injury (SCI) causes sensory dysfunctions such as paresthesia, dysesthesia, and chronic neuropathic pain. MiR-20a facilitates the axonal outgrowth of the cortical neurons. However, the role of miR-20a in the axonal outgrowth of primary sensory neurons and spinal cord dorsal column lesion (SDCL) is yet unknown. Therefore, the role of miR-20a post-SDCL was investigated in rat. The NF-200 immunofluorescence staining was applied to observe whether axonal outgrowth of dorsal root ganglion (DRG) neurons could be altered by miR-20a or PDZ-RhoGEF modulation in vitro. The expression of miR-20a was quantized with RT-PCR. Western blotting analyzed the expression of PDZ-RhoGEF/RhoA/GAP43 axis after miR-20a or PDZ-RhoGEF was modulated. The spinal cord sensory conduction function was assessed by somatosensory-evoked potentials and tape removal test. The results demonstrated that the expression of miR-20a decreased in a time-dependent manner post-SDCL. The regulation of miR-20a modulated the axonal growth and the expression of PDZ-RhoGEF/RhoA/GAP43 axis in vitro. The in vivo regulation of miR-20a altered the expression of miR-20a-PDZ-RhoGEF/RhoA/GAP43 axis and promoted the recovery of ascending sensory function post-SDCL. The results indicated that miR-20a/PDZ-RhoGEF/RhoA/GAP43 axis is associated with the pathophysiological process of SDCL. Thus, targeting the miR-20a/PDZ-RhoGEF /RhoA/GAP43 axis served as a novel strategy in promoting the sensory function recovery post-SCI.