S100A4在类风湿关节炎滑膜中的表达及其对成纤维样滑膜细胞分泌VEGF促进血管生成的影响  

Expression of S100A4 in synovium of patients with rheumatoid arthritis and its effect on angiogenesis of fibroblast-like synoviocytes by secreting VEGF

作　　者：查丁胜[1] 吴昊[1] 林宏生[1] 姚平[2] 查振刚[1] 贾春宏[3] 盛超[4] 

机构地区：[1]暨南大学附属第一医院骨科,广东广州510630 [2]暨南大学基础医学院生理教研室,广东广州510630 [3]南方医科大学基础医学院细胞生物学教研室 [4]南方医院妇产科,广东广州510515

出　　处：《中国病理生理杂志》2017年第6期1119-1124,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年项目(No.81401766);广东省医学科研基金(No.B2012196);暨南大学科研培育与创新基金青年基金(No.21612303);暨南大学附属第一医院培育基金(No.2012-1)

摘　　要：目的:研究S100钙结合蛋白A4(S100A4)在类风湿关节炎(rheumatoid arthritis,RA)患者和正常人膝关节滑膜中的表达水平,以及S100A4对类风湿关节炎成纤维样滑膜细胞(rheumatoid arthritis fibroblast-like synoviocytes,RAFLSs)促进血管生成的影响。方法:滑膜分别取自RA患者(RA组)及正常人(control组)膝关节,免疫组化法观察S100A4和VEGF蛋白在2组滑膜中的表达情况。RAFLSs分离自活动性RA滑膜;ELISA法检测S100A4刺激RAFLSs分泌血管内皮生长因子(vascular endothelial growth factor,VEGF)的作用;用rh S100A4孵育RAFLSs的条件培养基作用于人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs),检测S100A4体外血管生成能力。结果:S100A4及VEGF蛋白在RA组滑膜中高表达(P<0.05),rh S100A4显著刺激RAFLSs分泌VEGF,呈时间和剂量依赖性(P<0.05);rh S100A4孵育RAFLSs的条件培养基可促进HUVECs在体外形成管腔。结论:S100A4蛋白在RA患者膝关节滑膜中高表达,S100A4可通过促进RAFLSs分泌VEGF来刺激滑膜血管生成。这些结果提示S100A4可作为治疗RA的潜在靶点。AIM ： To study the expression level of S100 calcium-binding protein A4 （S100A4） in synovial tis-sue of the knee joint in rheumatoid arthritis （ RA） patients and normal persons, and the effect of S100A4 on the angiogene-sis induced by rheumatoid arthritis fibroblast-like synoviocytes （ RAFLSs）. METHODS ： The synovial tissue was taken from the knee joint of the RA patients （ RA group） and the normal persons （ control group）. The protein expression of S100A4 and vascular endothelial growth factor （VEGF） in the synovial tissue of the 2 groups was observed by immunohisto- chemistry. RAFLSs were isolated from synovial tissue of patients with active RA. ELISA was used to detect the effect of S100A4 on the secretion of VEGF by RAFLSs. The effect of S100A4 on the angiogenesis of HUVECs cultured with condi-tioned medium from RAFLSs was also detected. RESULTS ： The protein of S100A4 and VEGF was highly expressed in the synovial tissues of RA group （ P 〈 0. 05 ）. rhS100A4 significantly stimulated the secretion of VEGF in RAFLSs in a time- and dose-dependent manner （ P 〈0. 05）. Cultured with conditioned medium from RAFLSs, rhS100A4 significantly promo-ted HUVECs to form tube-like structures in vitro. CONCLUSION ： S100A4 protein is highly expressed in synovial tissue of the knee joint in RA patients, and S100A4 stimulates synovial angiogenesis by promoting RAFLSs to generate VEGF, indicating that S100A4 may be used as a potential target for the treatment of RA.

关 键 词：类风湿关节炎 S100钙结合蛋白A4 成纤维样滑膜细胞 血管生成 

分 类 号：R684.3[医药卫生—骨科学]