LncRNA-Anrel在类风湿关节炎中调控AnnexinⅠ的作用及机制研究

Svnovial Fibroblasts (SFs) and their expression of Annexin I have been proven to be of great importance in rheumatoid arthritis (RA) pathogenesis, however, the underlying mechanism remains unclear. Our previous study using long non-coding RNA (lncRNA) microarray have identified that lncRNA-Anrel is significantly increased in RA-SF. Further research have revealed that lncRNA-Anrel contains sequence identical to Annexin I and specific knock-down of lncRNA-Anrel expression could greatly reduce Annexin I expression, indicating that lncRNA-Anrel might contribute to RA pathogenesis through modulation on Annexxin I expression. This proposed study, on both cell and animal model levels, will in-depth investigate the mechanism underlying LncRNA-Anrel modulation of Annexin I expression and their impact to RA pathogenesis, as well as its efficacy as treatment target of rheumatoid arthritis. The anticipated outcome of the study will not only provide further understanding of RA pathogenesis, but also present potential target and route for RA treatment.

滑膜成纤维细胞（SF）及其表达的膜联蛋白I（Annexin I）在类风湿性关节炎（RA）的发生中发挥着重要作用，但目前具体机制尚未阐明。我们前期通过长链非编码RNA（lncRNA）芯片筛选发现：LncRNA-Anrel在RA-SF中的表达显著上调。进一步的研究发现，LncRNA-Anrel存在一段与Annexin I相同序列，且特异性抑制LncRNA-Anrel的表达能够显著降低Annexin I的水平，提示LncRNA-Anrel可能通过调控Annexin I来参与RA的病理进程。本申请拟在细胞水平和动物水平，深入研究LncRNA-Anrel调控Annexin I表达的机制、对RA病理功能的影响及LncRNA-Anrel/Annexin I信号通路作为靶标治疗RA的效果。预期的研究结果将进一步阐明RA的致病机制及为RA的治疗提供可能的途径和靶标。