Liu Xian Shuang, Chopp Michael, Pan Wan Long, Wang Xin Li, Fan Bao Yan, Zhang Yi, Kassis Haifa, Zhang Rui Lan, Zhang Xiao Ming, Zhang Zheng Gang
Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
Department of Physics, Oakland University, Rochester, MI, 48309, USA.
Mol Neurobiol. 2017 Jan;54(1):227-237. doi: 10.1007/s12035-015-9655-7. Epub 2016 Jan 6.
Stroke induces new myelinating oligodendrocytes that are involved in ischemic brain repair. Molecular mechanisms that regulate oligodendrogenesis have not been fully investigated. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression. MiR-146a has been reported to regulate immune response, but the role of miR-146a in oligodendrocyte progenitor cells (OPCs) remains unknown. Adult Wistar rats were subjected to the right middle cerebral artery occlusion (MCAo). In situ hybridization analysis with LNA probes against miR-146a revealed that stroke considerably increased miR-146a density in the corpus callosum and subventricular zone (SVZ) of the lateral ventricle of the ischemic hemisphere. In vitro, overexpression of miR-146a in neural progenitor cells (NPCs) significantly increased their differentiation into O4 OPCs. Overexpression of miR-146a in primary OPCs increased their expression of myelin proteins, whereas attenuation of endogenous miR-146a suppressed generation of myelin proteins. MiR-146a also inversely regulated its target gene-IRAK1 expression in OPCs. Attenuation of IRAK1 in OPCs substantially increased myelin proteins and decreased OPC apoptosis. Collectively, our data suggest that miR-146a may mediate stroke-induced oligodendrogenesis.
中风可诱导参与缺血性脑修复的新生髓鞘形成少突胶质细胞。调节少突胶质细胞生成的分子机制尚未得到充分研究。微小RNA（miRNA）是一类小的非编码RNA分子，可在转录后调节基因表达。据报道，miR-146a可调节免疫反应，但miR-146a在少突胶质前体细胞（OPC）中的作用尚不清楚。对成年Wistar大鼠进行右侧大脑中动脉闭塞（MCAo）手术。用针对miR-146a的锁核酸（LNA）探针进行原位杂交分析显示，中风显著增加了缺血半球侧脑室胼胝体和室下区（SVZ）中miR-146a的密度。在体外，神经前体细胞（NPC）中miR-146a的过表达显著增加了它们向O4 OPC的分化。原代OPC中miR-146a的过表达增加了其髓鞘蛋白的表达，而内源性miR-146a的减弱则抑制了髓鞘蛋白的生成。miR-146a还可反向调节其在OPC中的靶基因IRAK1的表达。OPC中IRAK1的减弱显著增加了髓鞘蛋白并减少了OPC凋亡。总的来说，我们的数据表明miR-146a可能介导中风诱导的少突胶质细胞生成。
