胶原诱导性关节炎大鼠淋巴细胞基因表达的变化

The Gene Expression Changes in Collagen-Induced Arthritis Rat Lymphocytes

研究胶原诱导性关节炎大鼠淋巴细胞基因表达谱,探讨类风湿性关节炎的发病机制。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淋巴细胞基因表达谱,比较模型大鼠及正常大鼠淋巴细胞基因表达的差异。结果显示,胶原诱导性关节炎大鼠差异表达基因822个,其中上调基因558个,下调基因264个。差异基因主要涉及功能基因为免疫应答及炎症刺激相关基因,涉及的代谢及信号通路主要有细胞凋亡、氧化应激、凝血系统、类花生酸合成、TGF信号通路等。模型组差异表达上调的基因主要有Ccr2、Ccr1、Il1b、Vcan、IgG-2a、Cyr61、Bmp8a、Tgfb1、RGD1564318等,差异表达下调的基因主要有Ifi27l1、Oas1a、G1p2、Sgk1、Irf7等。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。

Rheumatoid arthritis （RA） is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we studied collagen- induced arthritis rat lymphocyte genes profile expression. Using DNA microarray technique, the lymphocyte genes profile expression of the collagen-induced arthritis rats and the normal rats was compared. Lymphocytes were purified and total RNA was processed for a microarray analysis using Affymetrix Gene Chip technique. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that 822 genes expression of rats with collagen-induced arthritis were different compared with normal rats,including 558 up-regulated genes,and 264 down-regulated genes. Differential genes involved in the function group of immune response, inflammation stimulation, cell activation, carbohydrate binding and the pathway of apoptosis, oxidative stress ,eicosanoid synthesis ,blood clotting cascade ,prostaglandin synthesis regnlation,TGF beta signaling pathway and so on. The major overexpressed genes were Ccr2 （ chemokine receptor 2 ）, Ccrl （ chemokine receptor 1 ）, Ill b （ interleukin 1 beta）, Vcan （ versican）, IgG-2a（ gamma-2a immunoglobulin heavy chain）, Cyt61 （ cysteine-rich, angiogenie inducer ,61 ）, BmpSa （ bone morpho- genetic protein 8a）, Tgibl （ transforming growth factor, beta 1 ） and RGD1564318 （ similar to immunoglobulin light chain ） and the major underexpressed genes were Ifi2711 （ interferon, alpha-inducible protein 27 like）, Oasl a （ 2＇-5＇ oligoadenylate synthetase 1 A）, G1 p2 （ interferon, alpha-inducible protein）, Sgkl （ serum/glucocorticoid regulated kinase 1 ）, Irf7 （ interferon regulatory factor 7 ）. There are some genes which have been reported associated with RA in these differentia[ expression genes such as Cerl, Ccr2, Ill b, Vcan, Cyr61, CD44, Ieaml, TGF-~I, Hgf（ hepatoeyte growth factor）. And there are some differentia[ expression genes associated with RA which are first reported such as Mtdh（Metadhefin）,Ednra（ endothelin receptor type A）, Glp2. Our data indicate that the collagen-induced arthritis is a systemic immune disease involving multi-genes abnormal expression. The abnormal genes initially reflected the pathogenesis of rheumatoid arthritis, and provided important clues for the prevention and treatment.