胶原诱导性关节炎大鼠肝细胞基因表达的变化

Analysis on etiology and pathogenesis of rheumatoid arthritis by gene chip technology

目的通过研究胶原诱导性关节炎大鼠肝组织基因表达谱,探讨类风湿性关节炎的发病机制。方法采用d Chip(Dec.2009 version)分析软件lower bound fold change方法分析表达差异1.5倍以上基因,芯片类型为Gene Chip Rat Genome230,基因库为Affymetrix Gene,参考Gen Bank基因库,功能通路参考KEGG数据库。用大鼠全基因表达谱芯片研究胶原诱导性关节炎及正常大鼠肝组织基因表达谱,比较模型大鼠及正常大鼠肝组织基因表达的差异。结果结果显示,胶原诱导性关节炎大鼠差异表达基因有1 009个,其中上调基因480个,下调基因529个。差异表达基因主要涉及生物过程调控、刺激反应、细胞通信、细胞周期的负调控、免疫反应、应激反应、血管生成、内皮细胞分化等功能。涉及的代谢及信号通路主要有细胞凋亡通路、钙调节通路、TGF-β通路、凝血功能通路、炎症反应通路等通路。模型组差异表达上调的基因主要有Aldh1a7、Bad、Gdf10、Ccar2、Slc1a3、Il1b、Il7、Vegfb、Ig G-2a等,差异表达下调的基因主要有Ugt2b、Mx2、Usp18、Comt、Zfp354a、Oas1a、G1p2、Irf7等。结论胶原诱导性关节炎是一个涉及多基因表达异常的全身免疫性疾病,筛选到的差异表达基因初步反映了类风湿关节炎的发病机制,为类风湿关节炎的防治提供重要线索。

Objective To better understand pathogenesis of rheumatoid arthritis（RA） and to facilitate the search for novel RA therapeutics, we studied collagen-induced arthritis rat hepatic tissue genes profile expression. Methods Using DNA microarray technology, the hepatic tissue genes profile expression of the collagen-induced arthritis rats and the normal rats was compared. Hepatic tissue was purified and total RNA was processed for a m icroarray analysis using Affymetrix Gene Chip technology. Statistical comparison analysis identified differentially expressed genes that distinguished CIA from control rats. Results Clustering analysis indicated that 1009 genes expression of rats with collagen-induced arthritis were differences compared with normal rats, including 480 up-regulated genes and 529 down-regulated genes. Differential genes involved in the function group of regulation of cellular process, stimulation, cell communication, vasculature development, immune response, inflammation, and the pathway of apoptosis, oxidative stress, blood clotting cascade, TGF Beta signaling pathway, and so on. The major overexpressed genes were Aldh1a7, Bad, Gdf10, Ccar2, Slc1a3, Il1 b, Il7, Vegfb, and Ig G-2a, and the major underexpressed genes were Ugt2 b, Mx2, Usp18, Comt, Zfp354 a, Oas1 a, G1p2, and Irf7. Conclusion The collagen-induced arthritis is a systemic immune disease involving multi-genes abnormal expression. The abnormal genes could initially reflect the pathogenesis of rheumatoid arthritis, and provide important clues for the prevention and treatment of RA.