Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients.
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-kappaB = 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.
Nakamura
Nobuo
N
Center of Arthroplasty, Kyowakai Hospital, Suita, Japan.
Shimaoka
Yasunori
Y
Tougan
Takahiro
T
Onda
Hiroaki
H
Okuzaki
Daisuke
D
Zhao
Hanjun
H
Fujimori
Azumi
A
Yabuta
Norikazu
N
Nagamori
Ippei
I
Tanigawa
Akie
A
Sato
Jun
J
Oda
Takenori
T
Hayashida
Kenji
K
Suzuki
Ryuji
R
Yukioka
Masao
M
Nojima
Hiroshi
H
Ochi
Takahiro
T
D066258:Amphiregulin; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001854:Bone Marrow Cells / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000302:isolation & purification*; D066255:EGF Family of Proteins; D020869:Gene Expression Profiling / Q000379:methods*; D005796:Genes / Q000235:genetics; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007962:Leukocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology; D015854:Up-Regulation
C587848:AREG protein, human; D066258:Amphiregulin; D018076:DNA, Complementary; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins