Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous system demyelination.
Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous system demyelination.
复制标题
白细胞介素 7 受体 (IL-7R) 的下调会导致中枢神经系统脱髓鞘。
DOI：
10.18632/oncotarget.16081
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Lei X;Cai S;Chen Y;Cui J;Wang Y;Li Z;Li Y
白细胞介素7受体（IL-7 R）与多发性硬化（MS）的发病机制尚不清楚。由于髓鞘在斑马鱼和哺乳动物中的表达高度保守，斑马鱼已成为研究脱髓鞘的理想模型。我们使用转基因（Tg; mbp：nfsB-egfp）斑马鱼系，其中少突胶质细胞从幼虫期到成年期表达绿色荧光蛋白（GFP）。暴露成年转基因斑马鱼甲硝唑诱导的脱髓鞘，类似的形态学变化与MS的早期阶段。甲硝唑诱导的脱髓鞘被证实的磁共振成像（MRI）的第一次。微阵列分析显示IL-7 R在脱髓鞘过程中下调。靶向敲低IL-7 R表明，IL-7 R是胚胎和斑马鱼幼体髓鞘形成所必需的。此外，IL-7 R下调通过JAK/STAT途径诱导信号传导，导致少突胶质细胞凋亡。这些发现有助于我们了解IL-7 R在脱髓鞘中的作用，并为开发基于IL-7 R的MS和其他脱髓鞘疾病疗法提供了理论基础。
Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of multiple sclerosis (MS), though the mechanisms are not clear. Because myelin expression is highly conserved between zebrafish and mammals, zebrafish have become an ideal model for studying demyelination. We used a transgenic (Tg; mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult transgenic zebrafish to metronidazole induced demyelination that resembled the morphological changes associated with the early stages of MS. The metronidazole-induced demyelination was confirmed by magnetic resonance imaging (MRI) for the first time. Microarray analysis revealed down-regulation of IL-7R during demyelination. Targeted knockdown of IL-7R demonstrated that IL-7R is essential for myelination in embryonic and larval zebrafish. Moreover, IL-7R down-regulation induced signaling via the JAK/STAT pathway leading to apoptosis in oligodendrocytes. These findings contribute to our understanding of the role of IL-7R in demyelination, and provide a rationale for the development of IL-7R-based therapies for MS and other demyelinating diseases.