Increased phosphorylation of ezrin is associated with the migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
Increased phosphorylation of ezrin is associated with the migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
复制标题
埃兹蛋白磷酸化增加与类风湿关节炎患者成纤维样滑膜细胞的迁移和侵袭有关
DOI：
10.1093/rheumatology/keu013
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发表时间：
2014
期刊：
影响因子：
5.5
通讯作者：
Xu Hanshi
中科院分区：
文献类型：
--
作者：
Xiao Youjun;Sun Mengying;Zhan Zhongping;Ye Yujin;Huang Mingcheng;Zou Yaoyao;Liang Liuqin;Yang Xiuyan;Xu Hanshi
目的：越来越多的证据表明，细胞骨架蛋白埃兹蛋白可能在细胞运动中起关键作用。本研究旨在探讨ezrin在调节类风湿关节炎（RA）患者成纤维样滑膜细胞（FLS）迁移和侵袭中的作用。方法：取12例RA和6例OA患者的滑膜组织，分离FLS。用免疫印迹法或IF染色法检测ezrin和磷酸化ezrin（p-ezrin）的表达。使用ezrin磷酸化的特异性抑制剂和小干扰RNA介导的ezrin敲低来抑制ezrin的磷酸化。结果：与OA患者相比，RA患者滑膜组织和FLSs中p-ezrin蛋白表达明显增加。TNF-α和IL-1β刺激增加RA FLS中ezrin的磷酸化。通过ezrin磷酸化的特异性抑制剂和小干扰RNA介导的敲低来抑制p-ezrin蛋白减少RA FLS中的体外迁移和侵袭以及肌动蛋白应力纤维形成。rho激酶和p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路参与了ezrin的磷酸化和RA FLSs.Conclusion. P-ezrin的表达增加可能是RA FLSs异常侵袭行为的原因之一，这可能是由rho激酶和p38 MAPK信号通路介导的。这表明一种新的策略，靶向磷酸化ezrin，以防止滑膜侵袭和关节破坏类风湿关节炎。
Objective.Increasing evidence indicates that the cytoskeletal protein ezrin may play a critical role in cell motility. This study aims to investigate the role of ezrin in regulating the migration and invasion of fibroblast-like synoviocytes (FLSs) from patients with RA.Methods.Synovial tissues were obtained from 12 patients with RA and 6 with OA, and then FLSs were separated from synovial tissues. The expression of ezrin and phosphorylated ezrin (p-ezrin) was examined by Western blotting or IF staining. A specific inhibitor of ezrin phosphorylation and small interference RNA-mediated ezrin knockdown were used to inhibit the phosphorylation of ezrin. Migration and invasion of FLSsin vitrowere measured by the Boyden chamber assay.Results.Increased expression of p-ezrin protein was found in synovial tissue and FLSs in patients with RA compared with patients with OA. Stimulation with TNF-α and IL-1β increased ezrin phosphorylation in RA FLSs. Inhibition of p-ezrin protein by a specific inhibitor of phosphorylation of ezrin and small interfering RNA–mediated knockdown reducedin vitromigration and invasion, as well as actin stress fibre formation in RA FLS. Furthermore, rho kinase and p38 mitogen-activated protein kinase (MAPK) signal pathways were involved in the phosphorylation of ezrin and invasion of RA FLSs.Conclusion.Increased expression of p-ezrin may contribute to aberrant aggressive behaviours of RA FLSs, which are mediated by rho kinase and the p38 MAPK pathway. This suggests a novel strategy targeting phosphorylation of ezrin to prevent synovial invasiveness and joint destruction in RA.