Transcriptional profiling of microdissected areas of active multiple sclerosis lesions reveals activation of heat shock protein genes

Abstract

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.