Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush
Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush
复制标题
抑制 miR-21 可改善星形胶质细胞过度激活并促进视神经挤压后轴突再生
DOI：
10.1016/j.neuropharm.2018.04.028
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发表时间：
2018-07-15
影响因子：
4.7
通讯作者：
Feng, Dong-Fu
中科院分区：
文献类型：
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作者：
Li, Hong-Jiang;Pan, Yuan-Bo;Feng, Dong-Fu
视神经损伤是世界范围内不可逆视力损害的主要原因，甚至可能导致失明。星形胶质细胞的过度激活对视神经损伤后视网膜神经节细胞的修复和恢复有负面影响。然而，视神经损伤后星形胶质细胞激活的分子和细胞机制在很大程度上仍然未知。在本研究中，我们探讨了microRNA-21 （miR-21）对视神经损伤（ONC）大鼠模型中轴突再生和闪烁视觉诱发电位（F-VEP）的影响，以及基于星形胶质细胞激活的这些影响的潜在机制。据我们所知，本文首次报道了抑制miR-21可增强ONC大鼠模型中F-VEP的轴突再生并促进功能恢复。此外，抑制miR-21可以减弱过度的星形胶质细胞激活和胶质瘢痕形成，从而通过调节表皮生长因子受体（EGFR）途径促进轴突再生。此外，我们观察到miR-21的靶基因metalloproteinase-3的组织抑制剂的表达在此过程中被抑制。综上所述，这些发现表明，在ONC模型中，抑制miR-21可调节EGFR通路，改善星形细胞过度活化和胶质瘢痕进展，促进轴突再生，减轻F-VEP功能损伤。本研究结果表明，miR-21可能是视神经损伤的治疗靶点。(C) 2018 Elsevier Ltd.版权所有。
Optic nerve injury is a leading cause of irreversible visual impairment worldwide and can even cause blindness. Excessive activation of astrocytes has negative effects on the repair and recovery of retinal ganglion cells following optic nerve injury. However, the molecular and cellular mechanisms underlying astrocyte activation after optic nerve injury remain largely unknown. In the present study, we explored the effects of microRNA-21 (miR-21) on axon regeneration and flash visual evoked potential (F-VEP) and the underlying mechanisms of these effects based on astrocyte activation in the rat model of optic nerve crush (ONC). To the best of our knowledge, this article is the first to report that inhibition of miR-21 enhances axonal regeneration and promotes functional recovery in F-VEP in the rat model of ONC. Furthermore, inhibition of miR-21 attenuates excessive astrocyte activation and glial scar formation, thereby promoting axonal regeneration by regulating the epidermal growth factor receptor (EGFR) pathway. In addition, we observed that the expression of tissue inhibitor of metalloproteinase-3, a target gene of miR-21, was inhibited during this process. Taken together, these findings demonstrate that inhibition of miR-21 regulates the EGFR pathway, ameliorating excessive astrocyte activation and glial scar progression and promoting axonal regeneration and alleviating impairment in F-VEP function in a model of ONC. This study's results suggest that miR-21 may represent a therapeutic target for optic nerve injury. (C) 2018 Elsevier Ltd. All rights reserved.