Neurobiology of Disease (Apr 2005)

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

  • Jun-ichi Satoh,
  • Megumi Nakanishi,
  • Fumiko Koike,
  • Sachiko Miyake,
  • Toshiyuki Yamamoto,
  • Mitsuru Kawai,
  • Seiji Kikuchi,
  • Kyouichi Nomura,
  • Kazumasa Yokoyama,
  • Kohei Ota,
  • Takashi Kanda,
  • Toshiyuki Fukazawa,
  • Takashi Yamamura

Journal volume & issue
Vol. 18, no. 3
pp. 537 – 550

Abstract

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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.

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