Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium

Nobuyuki Watanabe; Kiichiro Ando; Shinichi Yoshida; Sawako Inuzuka; Masaaki Kobayashi; Nobuo Matsui; Takashi Okamoto

doi:10.1016/S0006-291X(02)00608-3

Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium

Biochem Biophys Res Commun. 2002 Jun 28;294(5):1121-9. doi: 10.1016/S0006-291X(02)00608-3.

Authors

Nobuyuki Watanabe¹, Kiichiro Ando, Shinichi Yoshida, Sawako Inuzuka, Masaaki Kobayashi, Nobuo Matsui, Takashi Okamoto

Affiliation

¹ Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.

PMID: 12074593
DOI: 10.1016/S0006-291X(02)00608-3

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Arthritis, Rheumatoid / genetics
Arthritis, Rheumatoid / metabolism*
Arthritis, Rheumatoid / pathology
Cell Division / drug effects
Cells, Cultured
Chemokine CXCL12
Chemokines, CXC / biosynthesis
Chemokines, CXC / genetics
DNA, Complementary / analysis
Female
Fibroblasts / drug effects
Fibroblasts / metabolism*
Gene Expression Profiling
Humans
Male
Middle Aged
Neoplasms / pathology
Oligonucleotide Array Sequence Analysis
Plasminogen Activator Inhibitor 1 / biosynthesis
Plasminogen Activator Inhibitor 1 / genetics
Platelet-Derived Growth Factor / pharmacology
RNA, Messenger / metabolism
Receptor, Platelet-Derived Growth Factor alpha / biosynthesis
Receptor, Platelet-Derived Growth Factor alpha / genetics
Reverse Transcriptase Polymerase Chain Reaction
Synovial Membrane / cytology
Synovial Membrane / metabolism*
Transcriptional Activation

Substances

CXCL12 protein, human
Chemokine CXCL12
Chemokines, CXC
DNA, Complementary
Plasminogen Activator Inhibitor 1
Platelet-Derived Growth Factor
RNA, Messenger
Receptor, Platelet-Derived Growth Factor alpha