信号素5A促进类风湿性关节炎血管翳形成的分子机制研究

类风湿性关节炎（RA）是以关节滑膜炎症为特征的全身慢性自身免疫性疾病，发病机制不明确。申请人前期研究发现SEMA5A在RA滑膜中表达升高，且与RA活动性相关。转录组测序及生物信息学分析发现SEMA5A参与细胞增殖与血管生成等生物学过程，提示其可能参与RA血管翳形成。相关结果已发表在Rheumatology（中科院二区）。在此基础上，本项目拟开展研究如下：1）大样本病例的回顾性和前瞻性实验研究进一步评估SEMA5A的临床诊断价值；2）体外、体内实验阐明SEMA5A对RA疾病进程（滑膜增生及血管翳形成）的影响及机制；3）筛选出与SEMA5A启动子序列结合的转录因子并对其进行验证，并揭示SEMA5A转录调控的分子机制。该项目研究旨在明确SEMA5A影响RA疾病进程的作用机制的基础上，为开发SEMA5A作为生物标志物用于RA临床诊断及药物干预靶点提供理论依据。

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by joint synovial inflammation, and the pathogenesis is unclear. The applicant's previous study found that the expression of SEMA5A was elevated in the synovial membrane of RA, and it was correlated with RA activity. Transcriptome sequencing and bioinformatics analysis showed that SEMA5A was involved in cell proliferation and angiogenesis, suggesting that SEMA5A may be involved in pannus formation of RA. Results were published in Rheumatology (Region 2, Chinese Academy of Sciences). On this basis, the research of this project is as follows: 1) Retrospective and prospective experimental studies on large sample cases to further evaluate the clinical diagnostic value of SEMA5A; 2) In vitro and in vivo experiments to elucidate the effect and mechanism of SEMA5A on the progression of RA (synovial hyperplasia and pannus formation); 3) Screen and verify the transcription factors binding to the SEMA5A promoter sequence and reveal the molecular mechanism of SEMA5A transcriptional regulation. This study aims to clarify the mechanism of SEMA5A's influence on the course of RA disease, and provide a theoretical basis for the development of SEMA5A as a biomarker for RA clinical diagnosis and drug intervention target.