TXNDC5编码蛋白质二硫键异构酶，在低缺氧状况下高表达，刺激细胞增殖和毛细血管增生。类风湿性关节炎（RA）关节滑膜呈现毛细血管增生和细胞增殖异常。我们首次发现TXNDC5在RA滑膜、患者血液中高表达，是RA易感基因，并在低氧条件下刺激RA炎症。该发现已发表SCI论文3篇，获9项专利授权。本课题计划（1）探索TXNDC5调控机制，用荧光素报告系统、染色体共沉淀、DNA测序分析①启动子结构、②低氧诱导机制、③3'UTR缺失及其与④RA临床表现的关系；（2）探索TXNDC5对RA作用的信号途径，①用蛋白质芯片探索对炎症、细胞凋亡、毛细血管增生的信号通路，②用siRNA方法探索低氧条件下对RA免疫的影响；（3）探索TXNDC5主动免疫和被动免疫对RA的作用，向TXNDC5过表达小鼠和knockout小鼠①注射TXNDC5短肽和②抗血清。本研究从RA的化学本质-低氧这一角度探索TXNDC5的作用。

Hypoxia is thought to stimulate synovial hypoperfusion in Rheumatoid arthritis (RA). TXNDC5 stimulates cell proliferation in hypoxic conditions. We previously detected increased TXNDC5 expression in synovial tissues and blood from patients with RA. We also found that the gene encoding TXNDC5 is susceptible to RA risk. In addition, we found that over-expressing TXNDC5 is susceptible for collagen II inducing arthritis (CIA) and stimulated adiponectin expression, cytokine production and cell proliferation and migration of fibroblasts of RA. This study aims to investigate the pathogenic roles of TXNDC5 in RA. Using chromatin immunoprecipitation, luciferase assay and DNA sequencing, we plan to clarify genomic structure of the TXNDC5 promoter；Using protein chip, we plan to understand the signal pathway of TXNDC5 on angiogenesis, cell proliferation and inflammation of RA； Using transgenic mice and CIA, we plan to understand the active immunity and passive immunity of TXNDC5 on RA.