| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MH7A(RCB1512) |
