論文 - 詳細
| RRC ID | 37687 |
|---|---|
| 著者 | Su J, Yu J, Ren T, Zhang W, Zhang Y, Liu X, Sun T, Lu H, Miyazawa K, Yao L. |
| タイトル | Discoidin domain receptor 2 is associated with the increased expression of matrix metalloproteinase-13 in synovial fibroblasts of rheumatoid arthritis. |
| ジャーナル | Mol Cell Biochem |
| Abstract |
Regulation of matrix metalloproteinase-13 (MMP-13) by collagen matrix in the synovial fibroblasts of rheumatoid arthritis (RA) is critical event in the progressive joint destruction. Our previous study indicated that a collagen receptor, discoidin receptor 2 (DDR2), was highly expressed in the synovial fibroblasts of RA. However, the functional role of DDR2 in the regulation of MMP-13 production in synovial fibroblasts has not been elucidated. In this study, we initially demonstrated that the DDR2 and MMP-13 proteins are both highly expressed in the synovial lining layer of RA. MMP-13 mRNA and protein in synovial fibroblasts of RA were preferentially induced by collagen type II compared with MMP-1. Furthermore, stable overexpression of wild type DDR2 in murine synoviocytes dramatically augments the production of MMP-13. The activation of DDR2 also mediates the up-regulation of MMP-13 promoter activity in 293T cells. Inhibitor specific for extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) cascade was shown to decrease MMP-13 level induced by collagen II in RA synovial fibroblasts and DDR2-induced MMP-13 promoter activity. Runx2 and activator protein-1 (AP-1) binding sites in MMP-13 promoter region are required for DDR2-induced transcription. The data in this study suggest that DDR2-mediated MMP-13 induction by collagen matrix in synovial fibroblasts of RA contributed to articular cartilage destruction. |
| 巻・号 | 330(1-2) |
| ページ | 141-52 |
| 公開日 | 2009-10-1 |
| DOI | 10.1007/s11010-009-0127-0 |
| PMID | 19415460 |
| MeSH | Animals Arthritis, Rheumatoid / pathology* Binding Sites Collagen Type II / pharmacology Discoidin Domain Receptors Extracellular Matrix Fibroblasts / pathology Humans Matrix Metalloproteinase 13 / genetics* Mice Receptor Protein-Tyrosine Kinases / genetics* Receptor Protein-Tyrosine Kinases / physiology* Receptors, Mitogen / genetics* Receptors, Mitogen / physiology* Synovial Membrane / pathology* Up-Regulation* |
| IF | 2.795 |
| 引用数 | 40 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |