Functional Genomic Analysis of Remyelination Reveals Importance of Inflammation in Oligodendrocyte Regeneration
Functional Genomic Analysis of Remyelination Reveals Importance of Inflammation in Oligodendrocyte Regeneration
复制标题
DOI：
10.1523/jneurosci.23-30-09824.2003
复制
发表时间：
2003-10
期刊：
影响因子：
--
通讯作者：
H. Arnett;Ying Wang;G. Matsushima;Kinuko Suzuki;J. Ting
中科院分区：
文献类型：
--
作者：
H. Arnett;Ying Wang;G. Matsushima;Kinuko Suzuki;J. Ting
肿瘤坏死因子α（TNFα）是一种促炎细胞因子，先前在脱髓鞘和髓鞘再生的小鼠模型中显示可促进髓鞘再生和少突胶质细胞前体增殖。我们在这项研究中使用Affyssin微阵列来鉴定（1）伴随脱髓鞘与髓鞘再生的基因表达变化，以及（2）野生型小鼠成功髓鞘再生与缺乏TNFα的小鼠不成功尝试髓鞘再生过程中基因表达的变化。炎性基因的改变代表了最显著的变化，在脱髓鞘、髓鞘再生过程中以及作为TNFα刺激的结果，小胶质细胞和星形胶质细胞中的主要组织相容性复合体（MHC）基因显著增强。然后使用缺乏微阵列鉴定的特定基因的小鼠进行研究，以检查这些基因在髓鞘再生中的作用。对MHC-II缺失小鼠的分析表明，少突胶质细胞的髓鞘再生和再生延迟，而去除MHC-I几乎没有影响。这些数据表明TNFα诱导MHC-II是髓鞘再生的重要调节事件，并强调了脑病理后再生中的主动炎症反应。
Tumor necrosis factor α (TNFα), a proinflammatory cytokine, was shown previously to promote remyelination and oligodendrocyte precursor proliferation in a murine model for demyelination and remyelination. We used Affymetrix microarrays in this study to identify (1) changes in gene expression that accompany demyelination versus remyelination and (2) changes in gene expression during the successful remyelination of wild-type mice versus the unsuccessful attempts in mice lacking TNFα. Alterations in inflammatory genes represented the most prominent changes, with major histocompatibility complex (MHC) genes dramatically enhanced in microglia and astrocytes during demyelination, remyelination, and as a consequence of TNFα stimulation. Studies to examine the roles of these genes in remyelination were then performed using mice lacking specific genes identified by the microarray. Analysis of MHC-II-null mice showed delayed remyelination and regeneration of oligodendrocytes, whereas removal of MHC-I had little effect. These data point to the induction of MHC-II by TNFα as an important regulatory event in remyelination and emphasize the active inflammatory response in regeneration after pathology in the brain.