EBP50对RA-FLS生物学行为的影响及其在RA发生发展中的作用和相关机制

Studies have confirmed that the abnormal proliferation and activation of RA-FLS play a key role in the process of arthropathy.Inhibiting it may be an effective method to control the development of RA.Many studies show that EBP50 is a powerful factor in inhibiting the abnormal tumor cell proliferation and activation,but the expression characteristics and function of EBP50 in RA-FLS have not yet been reported.In the previous study,we found for the first time that the expressions of EBP50 in RA-FLS was significantly lower and the EBP50-overexpression in RA-FLS can promote the cell apoptosis and inhibit the proliferation, which suggested that EBP50 can inhibit activation and proliferation of RA-FLS.However, the exact function、mechanism and significance in the development of RA is unknown.Based on the previous researches,we will construct and pack a recombinant lentiviral vector expression and interfering EBP50 firstly,then to explore the impacts and mechanisms of EBP50 on the biological behavior of RA-FLS,and the significance of EBP50 in the development of RA are planned to investigated at molecule,cell and animal model level. This study may discover the possibility of EBP50 to function as a new therapeutic target for RA,provide the theoretical and experimental foundation for its future application.

研究证实异常增殖的成纤维样滑膜细胞（FLS）在类风湿性关节炎（RA）的关节病变过程中发挥关键作用，抑制RA-FLS的异常活化和增殖是阻断或延缓RA进程的有效方法。EBP50是一种新近发现的肿瘤抑制因子，可有效抑制肿瘤细胞的增殖和侵袭能力，但其在FLS中的表达及功能尚未见报道。本课题组在前期研究中首次发现：EBP50在RA-FLS中的表达显著下调，且过表达EBP50可显著抑制RA-FLS的增殖并促进其凋亡，提示EBP50同样能够抑制RA-FLS的活化和增殖，但其确切的功能、机制及在RA发生发展中的意义不明。本项目拟在前期工作基础上，通过构建EBP50过表达和干扰慢病毒，分别在分子、细胞和RA动物模型水平探讨EBP50对RA-FLS生物学行为的影响及相关机制，以及其在RA发生发展过程中所发挥的作用和意义，以探讨EBP50作为RA新治疗靶标的可能性，为其将来可能的应用奠定理论和实验基础。

研究证实异常增殖的成纤维样滑膜细胞（FLS）在类风湿性关节炎（RA）的关节病变过程中发挥关键作用，抑制RA-FLS的异常活化和增殖是阻断或延缓RA进程的有效方法。EBP50是一种新近发现的肿瘤抑制因子，可有效抑制肿瘤细胞的增殖和侵袭能力，但其在FLS中的表达及功能尚未见报道。本课题组在研究中发现EBP50可显著抑制FLS的增殖而对自噬水平没有影响；同时发现EBP50可通过激活caspase-3以促进细胞凋亡；而且发现可显著抑制FLS的侵袭与迁移，其机制与下调MMP-9有关，但对MMP-2、E-cadherin和β-catenin表达水平无影响；EBP50还被发现可以下调IL-6和IL-8的分泌，证明其可减轻RA的炎症反应。本研究首次系统的探讨了EBP50对FLS的功能影响和相关机制研究，为EBP50作为RA新治疗靶标提供了依据，为其将来可能的应用奠定理论和实验基础。