Journal Article

Isolation and Expression Profiling of Genes Upregulated in Bone Marrow-Derived Mononuclear Cells of Rheumatoid Arthritis Patients

Nobuo Nakamura, Yasunori Shimaoka, Takahiro Tougan, Hiroaki Onda, Daisuke Okuzaki, Hanjun Zhao, Azumi Fujimori, Norikazu Yabuta, Ippei Nagamori, Akie Tanigawa, Jun Sato, Takenori Oda, Kenji Hayashida, Ryuji Suzuki, Masao Yukioka, Hiroshi Nojima and Takahiro Ochi

in DNA Research

Published on behalf of Kazusa DNA Research Institute

Volume 13, issue 4, pages 169-183
Published in print January 2006 | ISSN: 1340-2838
Published online January 2006 | e-ISSN: 1756-1663 | DOI: http://dx.doi.org/10.1093/dnares/dsl006

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We have comprehensively identified the genes whose expressions are augmented in bone marrow-derived mononuclear cells (BMMC) from patients with Rheumatoid Arthritis (RA) as compared with BMMCs from Osteoarthritis (OA) patients, and named them AURA after augmented in RA. Both stepwise subtractive hybridization and microarray analyses were used to identify AURA genes, which were confirmed by northern blot analysis and/or reverse transcription polymerase chain reaction (RT–PCR). We also assessed their expression levels in individual patients by quantitative real-time RT–PCR. Of 103 AURA genes we have identified, the mRNA levels of the following 10 genes, which are somehow related to immune responses, were increased in many of the RA patients: AREG (=AURA9), FK506-binding protein 5 (FKBP5 = AURA45), C-type lectin superfamily member 9 (CLECSF9 = AURA24), tyrosylprotein sulfotransferase 1 (TPST1 = AURA52), lymphocyte G0/G1 switch gene (G0S2 = AURA8), chemokine receptor 4 (CXCR4 = AURA86), nuclear factor-kappa B (NF-κB = AURA25) and two genes of unknown function (FLJ11106 = AURA1, BC022398 = AURA2 and XM_058513 = AURA17). Since AREG was most significantly increased in many of the RA patients, we subjected it to further analysis and found that AREG-epidermal growth factor receptor signaling is highly activated in synovial cells isolated from RA patients, but not in OA synoviocytes. We propose that the expression profiling of these AURA genes may improve our understanding of the pathogenesis of RA.

Keywords: stepwise subtraction; microarray; RA; OA; amphiregulin; synoviolin

Journal Article.  7076 words.  Illustrated.

Subjects: Genetics and Genomics

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