Wang Jingru, Chen Tuanzhi, Shan Guangzhen
Department of Neurology, Liaocheng People's Hospital, Liaocheng, China.
Front Cell Neurosci. 2017 Oct 20;11:329. doi: 10.3389/fncel.2017.00329. eCollection 2017.
Stroke is the second leading cause of death worldwide. Stroke induced proliferation and differentiation of neural stem cells (NSCs) that have been proven to participate in ischemic brain repair. However, molecular mechanisms that regulate neurogenesis have not been fully investigated. MicroRNAs play an important role in the neurological repairing process and impact stroke recovery outcome. MiRNA-148b has been reported to regulate cell proliferation in tumor cells, but its role in NSCs after ischemic stroke remains unknown. Here, we found an overexpression of MiRNA-148b in subventricular zone (SVZ) of rat ischemic brain. In original cultured ischemic NSCs, transfection of MiRNA-148b mimic or inhibitor could suppress or enhance the expression of Wnt-1, β-catenin, and Cyclin D1, hence effected wnt/β-catenin signaling. MiRNA-148b inhibitor promoted NSCs proliferation and differentiation into newborn neural and astrocytes, and this action could be silenced with knockdown of Wnt-1. In middle cerebral artery occlusion (MCAo) rats, injection of MiRNA-148b inhibitor could reduce ischemic lesion volume and improve neurological function outcome. Collectively, our data suggest that MiRNA-148b suppressed wnt/β-catenin signaling attenuates proliferation and differentiation of neural stem cells, these findings shed new light on the role of MiRNA-148b in the recovery process during the stroke and contribute to the novel therapy strategy.
中风是全球第二大致死原因。中风可诱导神经干细胞（NSCs）增殖和分化，且已证实这些细胞参与缺血性脑修复。然而，调节神经发生的分子机制尚未得到充分研究。微小RNA在神经修复过程中起重要作用，并影响中风恢复结果。据报道，MiRNA - 148b可调节肿瘤细胞中的细胞增殖，但其在缺血性中风后神经干细胞中的作用仍不清楚。在此，我们发现大鼠缺血性脑的脑室下区（SVZ）中MiRNA - 148b过表达。在原代培养的缺血性神经干细胞中，转染MiRNA - 148b模拟物或抑制剂可抑制或增强Wnt - 1、β-连环蛋白和细胞周期蛋白D1的表达，从而影响wnt/β-连环蛋白信号通路。MiRNA - 148b抑制剂促进神经干细胞增殖并分化为新生神经元和星形胶质细胞，且这种作用可通过敲低Wnt - 1而沉默。在大脑中动脉闭塞（MCAo）大鼠中，注射MiRNA - 148b抑制剂可减少缺血性损伤体积并改善神经功能结果。总体而言，我们的数据表明，MiRNA - 148b抑制wnt/β-连环蛋白信号通路会减弱神经干细胞的增殖和分化，这些发现为MiRNA - 148b在中风恢复过程中的作用提供了新见解，并有助于制定新的治疗策略。
