Zhou Songlin, Zhang Shibo, Wang Yaxian, Yi Sheng, Zhao Lili, Tang Xiaoyan, Yu Bin, Gu Xiaosong, Ding Fei
School of Biology and Basic Medical Sciences, Soochow University, Suzhou, JS 215123, PR China; Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Co-innovation Center of Neuroregeneration, 19 Qixiu Road, Nantong, JS 226001, PR China.
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Co-innovation Center of Neuroregeneration, 19 Qixiu Road, Nantong, JS 226001, PR China.
Neurosci Lett. 2015 Jan 23;586:43-9. doi: 10.1016/j.neulet.2014.12.006. Epub 2014 Dec 4.
MicroRNAs (miRNAs or miRs) are involved in phenotype modulation of neural cells after peripheral nerve injury. The effects of miRNAs on the survival of dorsal root ganglion (DRG) neurons, however, have not yet been well understood. In this study, microarray profiling indicated that 13 miRNAs were differentially expressed in rat DRGs (L4-L6) during the initial 7d period post sciatic nerve transection, and that the expressions of miR-21 and miR-222 (2 out of the 13 miRNAs) were continually increased over the time period. Tissue inhibitor of metalloproteinase 3 (TIMP3), a pro-apoptotic protein in various cancer cells, was identified as a common target of miR-21 and miR-222. Over-expression of miR-21 and miR-222 inhibited cell apoptosis and enhanced cell viability in cultured DRG neurons. IL-6 could induce up-regulation of miR-21 expression. All the results showed that miR-21 and miR-222 inhibited neuronal apoptosis at least partially through suppressing TIMP3 after peripheral nerve injury.
微小RNA（miRNA或miR）参与周围神经损伤后神经细胞的表型调节。然而，miRNA对背根神经节（DRG）神经元存活的影响尚未完全明确。在本研究中，微阵列分析表明，坐骨神经横断后最初7天内，大鼠DRG（L4-L6）中有13种miRNA表达存在差异，且miR-21和miR-222（这13种miRNA中的两种）的表达在该时间段内持续增加。金属蛋白酶组织抑制剂3（TIMP3）是各种癌细胞中的一种促凋亡蛋白，被确定为miR-21和miR-222的共同靶点。miR-21和miR-222的过表达抑制了培养的DRG神经元的细胞凋亡并增强了细胞活力。白细胞介素-6可诱导miR-21表达上调。所有结果表明，周围神经损伤后，miR-21和miR-222至少部分通过抑制TIMP3来抑制神经元凋亡。
