Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis

作者：Satoh J; Nakanishi M; Koike F; Miyake S; Yamamoto T; Kawai M; Kikuchi S; Nomura K; Yokoyama K; Ota K; Kanda T; Fukazawa T; Yamamura T^*

来源：Neurobiology of Disease, 2005, 18(3): 537-550.

DOI：10.1016/j.nbd.2004.10.007

• apoptosis
• gene expression profile
• microarray
• multiple sclerosis

To clarify the molecular mechanisms underlying multiple sclerosis (MS)-promoting autoimmune process, we have investigated a comprehensive gene expression profile of T cell and non-T cell fractions of peripheral blood mononuclear cells (PBMC) isolated from 72 MS patients and 22 age- and sex-matched healthy control (CN) subjects by using a cDNA microarray. Among 1258 genes examined, 173 genes in T cells and 50 genes in non-T cells were expressed differentially between MS and CN groups. Downregulated genes greatly outnumbered upregulated genes in MS. More than 80% of the top 30 most significant genes were categorized into apoptosis signaling-related genes of both proapoptotic and antiapoptotic classes. They included upregulation in MS of orphan nuclear receptor Nurr1 (NR4A2), receptor-interacting serine/threonine kinase 2 (RIPK2), and silencer of death domains (SODD), and downregulation in MS of TNF-related apoptosis-inducing ligand (TRAIL), B-cell CLL/lymphoma 2 (BCL2), and death-associated protein 6 (DAXX). Furthermore, a set of the genes involved in DNA repair, replication, and chromatin remodeling was downregulated in MS. These results suggest that MS lymphocytes show a complex pattern of gene regulation that represents a counterbalance between promoting and preventing apoptosis and DNA damage of lymphocytes.

• 出版日期2005-4