Research of the pathogenesis of arthritis rheumatoid by micro RNA and msearch of the possibility of a novel diagnosis method for arthritis rheumatoid by micro RNA

Micro RNA研究类风湿关节炎发病机制及Micro RNA诊断类风湿关节炎新方法的可能性研究

• 批准号: 18591109
• 负责人: NAKAMACHI Yuji
• 金额: $ 2.55万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591109/
• 关键词: Rheumatoid arthritis; Micro RNA

Rheumatoid arthritis (RA) is a chronic disease of unknown etiology that presents a characteristic constellation of features that includes infiltrating leukocytes to synoviocytes and synoviocyte hyperplasia, resulting in pannus formation and joint destruction. The local production of cytokines and chemokines by these cells accounts for many of the pathological and clinical manifestations of RA. The molecular marker which could diagnose early RA or predict the response to currently used treatments does not exist.Our aim was to reveal the pathogenesis of RA by analyzing the expression of micro RNA (miRNA), a novel RNA interfence factor, and to exploit the possibility of inventing a novel diagnostic method and a novel therapy.One of the research foci was the identification of the specific miRNAs to RA fibroblast-like synoviocyte (RA-FIS). We found that five miRNAs were more strongly expressed in RA-FLS than in osteoarthritis FIS (0A-FLS), and miR-124a was the only significantly decreased miRNA in RA-FLS as compared to OA-FLS. The transfection of a precursor of miR-124a into RA-FLS suppressed their proliferation significantly and forced to stop the cell cycle at G1 phase with no significant increase of apoptosis to RA-FLS. We identified a putative consensus site for miR-124a binding in the 3UTR regions of CDK2 and MCP1 mRNA, and induction of miR-124a into RA-FLS significantly suppressed the production of CDK2 and MCP1 proteins. These results suggest that decreasing miR-124a expression in RA-FLS is deeply involved in the pathogenesis of RA.Another research focus was to identify the RA-specific miRNAs in peripheral blood mononuclear cells (PBMC). We have been searching for RA-specific miRNA in PBMC, and preliminary data show that totally different sets of miRNAs from that of RA-FLS are anticipated.All research expenses were spent to buy chemical reagents and disposable equipments.

风湿性关节炎（RA）是一种病因不明的慢性疾病，其特征包括白细胞浸润至滑膜细胞和滑膜细胞增生，导致血管翳形成和关节破坏。这些细胞局部产生的细胞因子和趋化因子解释了RA的许多病理和临床表现。目前尚不存在能早期诊断RA或预测RA治疗效果的分子标志物，本研究旨在通过分析RA患者外周血中一种新的RNA干扰因子microRNA（miRNA）的表达，目前的研究热点之一是鉴定RA成纤维样滑膜细胞特异性miRNAs（RA-FIS）。我们发现5种miRNA在RA-FLS中的表达比在骨关节炎FIS（0A-FLS）中更强，并且miR-124 a是与OA-FLS相比在RA-FLS中唯一显著降低的miRNA。转染miR-124 a前体基因后，RA-FLS细胞的增殖明显受到抑制，细胞周期停滞于G1期，凋亡率无明显增加。我们在CDK 2和MCP 1 mRNA的3UTR区域中鉴定了miR-124 a结合的推定共有位点，并且将miR-124 a诱导到RA-FLS中显著抑制了CDK 2和MCP 1蛋白的产生。这些结果提示miR-124 a在RA FLS中表达的降低与RA的发病机制密切相关。另一个研究热点是在外周血单个核细胞（PBMC）中鉴定RA特异性miRNA。我们一直在PBMC中寻找RA特异性的miRNA，初步数据显示，我们可以在PBMC中找到与RA-FLS完全不同的miRNA。