外泌体mRNA调节Wnt通路对关节滑膜增殖、炎症的作用及其机制

类风湿关节炎（RA）是一种病因未明的慢性系统性自身免疫性疾病，我们前期3个国家自然科学基金研究结果显示：与增殖密切相关的Wnt通路在RA滑膜炎症、骨侵蚀及软骨破坏方面发挥重要调控作用。新近发现RA血清外泌体mRNA与正常人有所差异，其中Wnt通路中的多个分子mRNA均存在显著差异。故本研究在上述研究基础上拟开展：①明确Wnt通路分子mRNA在RA患者血清外泌体和FLS外泌体中的表达情况。②从基因和蛋白层面探讨外泌体Dvl3 mRNA对滑膜细胞增殖、凋亡及炎症反应的影响。③观察外泌体Dvl3 mRNA对TNF-α转基因关节炎小鼠模型滑膜炎症的影响。④探讨外泌体Dvl3 mRNA调节Wnt通路在RA发生发展中的作用机制。步步深入，紧密相连，全面阐释了外泌体mRNA调节Wnt通路在类风湿关节炎滑膜增殖、炎症反应中的作用及机制，为新型药物类型研发提供了可靠的理论依据，为未来治疗RA增添了新的靶点。

Rheumatoid arthritis is a chronic systemic autoimmune disease of unclear cause. Our previous three National Natural Science Foundation research results show: Wnt pathway, closely related to the proliferation, plays an important regulatory role in synovial inflammation, bone erosion and cartilage destruction of rheumatoid arthritis (RA). The serum exosome mRNA in patients with RA is newly discovered different from that in normal people, and there are significant differences in several mRNAs in Wnt pathway. Therefore, based on the previous studies, we will carry out following work in this study: ①To clarify the differential expression of mRNA of exosomes in patients with RA and in FLS. ②To explore the function of Dvl3 mRNA to synovial cell proliferation, apoptosis and inflammatory reaction on the gene and protein levels. ③To verify the regulatory role of Dvl3 mRNA in TNF-α transgenic mouse model of arthritis. ④ To deeply study the molecular mechanisms of exosomal Dvl3 mRNA through the Wnt pathway in RA. This study comprehensively expound the function and mechanism of exosomal Dvl3 mRNA regulating Wnt pathway in RA synovial proliferation and inflammatory response on the level of clinical samples, primary cells, genes, proteins, vitro and vivo, and to provide a new reliable theoretical basis for the development of new drugs and add a new target for the future treatment of RA.