Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium.
To elucidate the aberrant growth properties of rheumatoid synoviocytes, we have examined the gene expression profile of rheumatoid synovial fibroblasts (RSFs) and compared with that of normal synovial fibroblasts (NSF). Gene expression profile analysis was conducted with synoviocyte cultures obtained from five rheumatoid arthritis (RA) patients and five control cases using a commercial cDNA array containing the defined 588 cancer-related genes. The results were confirmed by real-time RT-PCR. Gene expression levels for the platelet-derived growth factor receptor alpha (PDGFRalpha), plasminogen activator inhibitor-1 (PAI-1), and stromal cell derived factor 1A (SDF1A) are constitutively augmented in RSF compared with NSF. The mRNA levels of PDGFRalpha, PAI-1, and SDF1A in RSF over NSF were 4.6-, 14-, and 2.8-fold, respectively, by real-time RT-PCR. In fact, we found that RSFs showed greater sensitivity to the cell proliferative effect of PDGF. T his aberrant gene expression profile suggests that RSF may have retained the premature phenotype of primordial synoviocytes.
Watanabe
Nobuyuki
N
Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
Ando
Kiichiro
K
Yoshida
Shinichi
S
Inuzuka
Sawako
S
Kobayashi
Masaaki
M
Matsui
Nobuo
N
Okamoto
Takashi
T
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D015533:Transcriptional Activation
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D018076:DNA, Complementary; D017395:Plasminogen Activator Inhibitor 1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha