Resistin/miR-324-3p/IL-18在滑膜细胞参与类风湿性关节炎（RA）炎症反应中的作用机制

控制血管新生与炎症反应可有效缓解类风湿性关节炎（RA）。我们已阐明抵抗素（Resistin）在调控RA血管新生的作用及机制，近期，我们又发现Resistin可刺激滑膜细胞分泌IL-18参与炎症反应，但调控机制尚不清楚。经预实验发现，Resistin刺激后的滑膜细胞中，miR-324-3p显著降低，而IL-18浓度显著升高，推测：Resistin/miR-324-3p/IL-18可调控滑膜细胞参与RA炎症反应。本项目拟在明确Resistin具有促IL-18分泌基础上，对miR-324-3p进行基因调控，阐明Resistin的作用机制，并利用中和性单抗评价以Resistin为RA靶点的治疗效果。我们预测：Resistin负调控miR-324-3p，进而促进滑膜细胞分泌IL-18参与炎症反应。本研究将有助于深入了解RA的发病机制，也为临床干预RA的炎症反应与血管新生寻求新的药物靶点提供理论依据。

A strategy of regulation to angiogenesis and inflammation is effective against rheumatoid arthritis (RA) progression. Our previous report has demonstrated the role of resistin regulating angiogenesis and signaling pathway in RA. However, the mechanism by which resistin induced IL-18 inflammation in synovial fibroblasts is still unclear. The aim of this project is to explore that resistin induced the expression of IL-18 secreted from synovial fibroblasts through miR-324-3p negatively regulating. Our preliminary data showed that resistin significantly decreased microRNA-324-3p (miR-324-3p) expression and increased interleukin-18 (IL-18) expression in synovial fibroblasts in vitro. As inflammatory effects upon synovial fibroblasts of resistin in vitro, we would further evaluate the role of resistin in vivo. We used resistin neutralized antibody to interfere with RA pathogenic process in collagen-induced arthritis mice model. In addition, we also developed in vivo angiogenic model by using chick chorioallantoic membrane assay to examine the relationship between resistin and the specimens of RA patients Above results will help us to understand the complicated RA pathogenesis by inflammation and angiogenesis so that resistin might become a therapeutic target of RA.