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

发布时间：2018-09-11 09:38

【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(P0.05),rh S100A4显著刺激RAFLSs分泌VEGF,呈时间和剂量依赖性(P0.05);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。
[Abstract]:Aim: to investigate the expression of S100 calcium binding protein A4 (S100A4) in synovium of knee joint in patients with rheumatoid arthritis (rheumatoid arthritis,RA) and normal subjects, and the effect of S100A4 on angiogenesis in fibroid synovial cells (rheumatoid arthritis fibroblast-like synoviocytes,RAFLSs) of rheumatoid arthritis (RA). Methods: synovial membrane was obtained from knee joint of RA patients (RA group) and normal subjects (control group). The expression of S100A4 and VEGF protein in synovium of two groups was observed by immunohistochemical method. RAFLSs isolated from active RA synovial membrane was used to detect the effect of S100A4 on the secretion of vascular endothelial growth factor (vascular endothelial growth factor,VEGF) by RAFLSs. Human umbilical vein endothelial cells (human umbilical vein endothelial cells,HUVECs) were incubated with RAFLSs conditioned medium (rh S100A4), and the angiogenesis ability of S100A4 in vitro was measured. Results the high expression of VEGF protein and S100A4 protein in the synovium of RA group (P0.05) significantly stimulated RAFLSs to secrete VEGF, in a time-and dose-dependent manner (P0.05). The conditioned medium of RAFLSs incubated with Rh S100A4 could promote the formation of HUVECs in vitro. Conclusion the high expression of S100A4 protein in synovial membrane of patients with RA can stimulate synovial angiogenesis by promoting the secretion of VEGF by RAFLSs. These results suggest that S100A4 may be a potential target for the treatment of RA.
【作者单位】：暨南大学附属第一医院骨科;暨南大学基础医学院生理教研室;南方医科大学基础医学院细胞生物学教研室;南方医科大学南方医院妇产科;
【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)
【分类号】：R593.22

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