論文 - 詳細
| RRC ID | 17682 |
|---|---|
| 著者 | Fujishiro M, Nozawa K, Kawasaki M, Yamaguchi A, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Fukui H, Kaneko K, Ogawa H, Takamori K, Takasaki Y, Sekigawa I. |
| タイトル | Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid arthritis. |
| ジャーナル | Mod Rheumatol |
| Abstract |
INTRODUCTION:A protein analysis using mass spectrometry revealed the existence of serum proteins with significant quantitative changes after the administration of infliximab. Among these proteins, regenerating gene (REG) 1α appears to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, the present study was conducted to examine the mechanism of REG1α in RA disease progression. METHODS:Serum samples were collected from RA patients and normal healthy controls. REG1α expression was evaluated by ELISA, RT-PCR, and indirect immunofluorescence microscopy. The functions of REG1α on synovial fibroblasts with regard to apoptosis, receptor activator of NF-κB ligand (RANKL) expression, and cellar proliferation were evaluated using siRNA to inhibit the intrinsic REG1α mRNA expression. RESULTS:The serum concentrations of REG1α in RA patients were higher than in normal healthy controls. The high expression of REG1α was also observed in the synovial tissue of RA patients compared to those of osteoarthropathy patients. In addition, tumor necrosis factor-α (TNF-α) upregulated REG1α expression in the synovial fibroblasts cell line (MH7A). Inhibition of REG1α expression suppressed the induction of RANKL expression by TNF-α. Furthermore, exogenous recombinant REG1α protein inhibited apoptosis and promoted cell proliferation in MH7A cells. These effects were abolished in the REG1α-siRNA MH7A cells. CONCLUSION:The present data suggest that TNF-α induces aberrant REG1α expression and that REG1α plays an important role in aberrant cell proliferation and RANKL expression of synovial fibroblasts, ultimately resulting in pannus formation. Restoration of normal physiological REG1α expression may contribute to disease amelioration. |
| 巻・号 | 22(2) |
| ページ | 228-37 |
| 公開日 | 2012-4-1 |
| DOI | 10.1007/s10165-011-0564-y |
| PMID | 22203215 |
| MeSH | Apoptosis / drug effects Arthritis, Rheumatoid / blood Arthritis, Rheumatoid / diagnosis Arthritis, Rheumatoid / genetics* Cell Line Cell Proliferation / drug effects Disease Progression Female Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Gene Expression Gene Silencing Granulation Tissue / metabolism Granulation Tissue / pathology Humans Lithostathine / blood Lithostathine / genetics* Lithostathine / pharmacology Male RANK Ligand / metabolism RNA, Small Interfering / genetics Recombinant Proteins Synovial Membrane / metabolism Synovial Membrane / pathology Tumor Necrosis Factor-alpha / pharmacology |
| IF | 2.113 |
| 引用数 | 4 |
| WOS 分野 | RHEUMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |