Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic acid down-regulate MMPs in rheumatoid arthritis
Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic acid down-regulate MMPs in rheumatoid arthritis
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DOI：
10.1007/s00296-011-1960-5
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发表时间：
2012-09
影响因子：
4
通讯作者：
Jian‐guang Wang;J. Ruan;Chun-yang Li;Jian-min Wang;Yan Li;Weitao Zhai;Wei Zhang;H. Ye;Nian-han Shen;K. Lei;Xiuling Chen;Xin-yu Yang
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文献类型：
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作者：
Jian‐guang Wang;J. Ruan;Chun-yang Li;Jian-min Wang;Yan Li;Weitao Zhai;Wei Zhang;H. Ye;Nian-han Shen;K. Lei;Xiuling Chen;Xin-yu Yang
10-羟基-2-癸烯酸(10H2 DA)通过丝裂原活化蛋白激酶信号通路激活基质金属蛋白酶(MMPs)，有望成为治疗类风湿关节炎(RA)的药物。本工作的目的是通过比较蛋白质组学分析，寻找类风湿关节炎滑膜成纤维细胞(RASF)经10H2 DA处理后的差异表达蛋白质。采用双向电泳法(2-DE)和LC-MS/MS法检测10H_2DA处理24小时后蛋白质表达的变化。用实时荧光定量聚合酶链式反应和Western印迹分析鉴定差异表达蛋白。应用RNAi技术研究结缔组织生长因子(CTGF)表达下调对MMPs的影响。处理24小时后，10个蛋白质表达上调，9个蛋白质表达下调。共有19个差异表达的蛋白质被鉴定，并被发现与糖酵解、脂代谢、细胞黏附、ATP合成、氧化还原和抗凋亡相关。CTGF是C端富含半胱氨酸蛋白(CCN)家族的一员，经10H2DA处理24小时后，CTGF表达下调。RNAi(CTGFi)后MMPs表达下调。这些结果表明，CTGF是MMPs表达的调节因子，10H2 DA可能通过下调CTGF的表达来下调MMPs的浓度。
10-hydroxy-2-decenoic acid (10H2DA) is suggested to be a potential medication for rheumatoid arthritis (RA) by activation of matrix metalloproteinases (MMPs) via mitogen-activated protein kinase signaling pathways. The aim of the present work was to seek differentially expressed proteins in rheumatoid arthritis synovial fibroblasts (RASFs) treated with 10H2DA by comparative proteomics analysis. Two-dimensional electrophoresis (2-DE) and LC–MS/MS were performed to identify changes in protein expression after 24-h 10H2DA treatment. Differentially expressed proteins were identified by real-time PCR and Western blot analysis. Influence of down-regulation of connective tissue growth factor (CTGF) expression on MMPs was studied by RNAi. Ten proteins were up-regulated and 9 proteins were down-regulated after 24-h 10H2DA treatment. A total of 19 differentially expressed proteins were identified and found to be associated with glycolysis, lipid metabolism, cell adhesion, ATP synthesis, oxidation reduction, and anti-apoptosis. CTGF, a member of the C-terminal cystein-rich proteins (CCN) family, was down-regulated after 24-h 10H2DA treatment. MMPs were down-regulated after RNAi (CTGFi). These results suggest that CTGF is a regulator factor in the expression of MMPs, and 10H2DA down-regulate the concentration of MMPs probably by down-regulating the expression of CTGF.