Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
J Neurosci Res. 2012 Oct;90(10):1941-8. doi: 10.1002/jnr.23079. Epub 2012 Jun 20.
Heat shock proteins (HSPs) are stress-responsive proteins that serve as important molecules contributing to cellular "protein triage." We and others have reported an increase of selected HSPs in multiple sclerosis (MS) lesions. However, the exact expression pattern of HSP family genes in MS is not known. The aim of our research was to assess global transcriptional changes of all gene members of the HSP families within MS lesions and associated normal-appearing white matter (NAWM). To this end, we used laser capture microdissection (LCM) to isolate defined regions of chronic-active MS lesions (n = 5), one of the most common types of MS lesions. To identify changes in HSP genes in relation to different areas of the plaque, we used genome-wide microarray analysis. We detected a significant change in the transcriptional profile of the demyelinated region compared with NAWM. In particular, overall expression of different HSP genes was upregulated in different areas of chronic-active lesion. These changes were linked to an upregulation of heat shock factor 4 (HSF4). This is the first global analysis of transcriptional changes in HSPs in the central nervous system during MS. The results support a relationship between HSP activation and lesion activity.
热休克蛋白（HSPs）是应激反应蛋白，作为细胞“蛋白质分类”的重要分子。我们和其他人已经报道了在多发性硬化症（MS）病变中选定 HSP 的增加。然而，MS 中 HSP 家族基因的确切表达模式尚不清楚。我们研究的目的是评估 MS 病变和相关正常外观白质（NAWM）中 HSP 家族所有基因成员的全局转录变化。为此，我们使用激光捕获显微切割（LCM）来分离慢性活跃 MS 病变（n = 5）的定义区域，这是 MS 病变最常见的类型之一。为了确定 HSP 基因与斑块不同区域的变化，我们使用全基因组微阵列分析。与 NAWM 相比，我们检测到脱髓鞘区域转录谱的显著变化。特别是，慢性活跃病变不同区域的不同 HSP 基因的总体表达上调。这些变化与热休克因子 4（HSF4）的上调有关。这是 MS 期间中枢神经系统中 HSP 转录变化的首次全面分析。结果支持 HSP 激活与病变活性之间的关系。
