Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.
Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.
复制标题
胶原诱导关节炎中转录因子 SOX5 部分通过调节 MMP-9 表达促进成纤维样滑膜细胞的迁移和侵袭
DOI：
10.3389/fimmu.2018.00749
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Shi Y;Wu Q;Xuan W;Feng X;Wang F;Tsao BP;Zhang M;Tan W
Objectives Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. Methods The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Results Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. Conclusion SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.
登录
查看更多内容
DOI：
10.1084/jem.20130791
发表时间：
2014-08-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Tanaka S;Suto A;Iwamoto T;Kashiwakuma D;Kagami S;Suzuki K;Takatori H;Tamachi T;Hirose K;Onodera A;Suzuki J;Ohara O;Yamashita M;Nakayama T;Nakajima H
通讯作者：
Nakajima H
影响因子：
6.4
作者：
Ma, Stephanie;Chan, Yuen Pin;Chan, Kwok Wah
通讯作者：
Chan, Kwok Wah
DOI：
10.1073/pnas.0806791105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Kwan, Kenneth Y.;Lam, Mandy M. S.;Sestan, Nenad
通讯作者：
Sestan, Nenad
SOX5通过调节肝细胞癌中的Twist1促进上皮-间质转化和细胞侵袭
影响因子：
3.4
作者：
Wang, Dong;Han, Sheng;Li, Xiangcheng
通讯作者：
Li, Xiangcheng
影响因子：
5.3
作者：
Han, Yu;Lefebvre, Veronique
通讯作者：
Lefebvre, Veronique