LncRNA H19通过海绵吸附miR-130调控FGF-8/BMP-2 在类风湿关节炎成纤维样滑膜细胞中的机制研究

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis and high disability rate. Long noncoding RNA H19 has always been considered as a regulatory factor in the growth of tumor only. Recent studies have shown that the expression of lncRNA H19 in synovial tissue of RA patients was significantly upregulated, but the exact function and mechanism remains unclear. In this study, we verified the expression level of lncRNA H19 in synovial tissue and fibroblast-like synoviocytes (FLS) of RA, osteoarthritis and normal trauma patients by RT-PCR. Then we transfected with lncRNA H19 siRNA in RA-FLS to investigate the expression of FGF-8 and BMP-2 and inflammatory cytokines secretion and analyze the interaction between lncRNA H19 and miR-130 by bioinformatics software, RNA immunoprecipitation and dual luciferase assay. Lastly, we explored the mechanism of lncRNA H19 in regulating bone metabolism disorder of RA. The study will clarify the role of lncRNA H19 in the development and progression of RA, which is important for identifying the pathogenesis of synovitis and finding effective target of gene therapy in RA.

类风湿关节炎（RA）是以关节滑膜炎为主要特征的慢性自身免疫性疾病，具有较高的致残率。lncRNA H19一直被认为只在肿瘤的发生、生长中有调节作用。近来研究表明RA患者的滑膜组织中lncRNA H19表达显著上调，其确切功能和作用机制尚不清楚。本课题拟通过 RT-PCR 技术验证RA、骨关节炎和正常创伤患者的滑膜组织和成纤维样滑膜细胞（FLS）中lncRNA H19的表达水平，随后在RA-FLS中应用siRNA干扰lncRNA H19表达，研究其对RA-FLS的FGF-8、BMP-2表达和炎症因子分泌等生物学行为的影响，同时通过生物信息软件预测、RNA免疫共沉淀和双荧光素酶实验，分析lncRNA H19与miR-130的作用关系，明确lncRNA H19调控RA骨代谢紊乱的作用机制。本课题研究结果将阐明lncRNA H19在RA发生发展中的作用，以期明确RA关节滑膜炎症的发病机制和找到有效的基因治疗靶点。

类风湿关节炎（RA）是一种以关节滑膜炎症为主要特征的慢性自身免疫性疾病，近来研究表明RA患者的滑膜组织中lncRNA H19表达显著上调，但其确切功能和作用机制尚不清楚。在本项目的资助下，我们研究了RA和骨关节炎（OA）患者滑膜组织和成纤维样滑膜细胞（FLS）中lncRNA H19的表达，应用siRNA干扰lncRNA H19表达探究了其对RA-FLS增殖、迁移、侵袭及炎症因子的表达，同时通过生物信息软件预测和双荧光素酶报告基因实验，明确了lncRNA H19与miR-130的相互作用关系，探索了lncRNA H19调节骨代谢紊乱的具体机制。该项目重要结果包括：证实了RA患者的滑膜组织和FLS中lncRNA H19显著高表达；抑制RA-FLS中lncRNA H19的表达可以明显抑制其增殖、迁移、侵袭和炎症因子表达；lncRNA H19通过海绵吸附miR-130b促进FGF-8的表达，抑制BMP-2的表达，促进RA患者FLS细胞的增殖、迁移和侵袭。这些研究结果提示：lncRNA H19通过海绵吸附miR-130b破坏了骨代谢平衡紊乱，加重滑膜炎的发生发展，从而为类风湿关节炎的早期诊断和基因治疗靶点提供有力的依据。