类风湿关节炎患者滑膜成纤维细胞基因表达的公共数据分析  

Whole-genome expression analysis of synovial fibroblasts in rheumatoid arthritis

作　　者：刘珂[1] 侯毅[1] 郑稼[1] 

机构地区：[1]河南省人民医院骨科,郑州450003

出　　处：《中华骨科杂志》2017年第11期691-697,共7页Chinese Journal of Orthopaedics

摘　　要：目的探讨膝关节滑膜成纤维细胞在类风湿关节炎发生、发展过程中的作用及在发病过程中起重要作用的通路。方法在公共数据库NCBIGEO和EBI Array Express中，通过查找关键字进行数据检索，筛选出符合要求的全基因组表达谱芯片数据。对收集到的mRNA芯片表达谱数据进行整合，采用GeneSpring软件进行数据的归一化，通过SAM方法确定差异表达基因和差异表达倍数。使用在线工具DAVID和STRING对差异表达基因进行功能富集和互作分析。结果通过数据检索共发现符合要求的公共数据集2个，比较患者和健康人群膝关节滑膜成纤维细胞的表达谱后确定显著差异表达基因336个，其中患者组显著下调基因261个、显著上调基因75个。细胞外基质的编码基因占所有显著下调基因的13．6％。透明软骨的重要成分COL9A3，组成基底膜的COL4A5，以及WNT基因家族成员WNT2、WNT11、WNT16都有不同程度的表达下降。能够降解Ⅱ型胶原的基质金属蛋白酶13（matrix metalloproteinase 13，MMP13）表达量显著上调，它可能直接参与了软骨组织降解，也可能与其他蛋白互作来调节细胞生长。结论通过对公共数据的挖掘揭示了细胞外基质降解在类风湿关节炎病情发展中的重要作用：MMP13、WNT2、WNT11、WNT16、COL9A3、COL4A5与细胞外基质、软骨关节合成、降解有关的基因可能成为类风湿关节炎治疗的靶标。Objective To identify the crucial gene implicated in rheumatoid arthritis （RA） pathogenesis by comparing microarray-based gene expression profiles of synovial fibroblast in arthritis patients and that in control. Methods The public datasets were obtained from NCBI GEO and EBI ArrayExpress. The qualified microarray-based gene expression profiles were inte- grated and normalized using the method implemented in GeneSpring software. Furthermore, the differentially expressed genes （DEGs） were identified using significance analysis of microarrays （SAM） method. The online tool DAVID and STRING were applied to conduct the enrichment analysis and gene product interaction analysis respectively. Results There were two datasets that were qualified and analyzed in the present study. A total of 336 significant DEGs were identified by comparing the whole-genome gene expression profiles from synovial fibroblast of RA patients and control group. Among these DEGs, 261 were significantly downregulated and 75 upregulated. About 13.6% of the downregulated genes were associated with extracellular matrix degradation. The COL9A3 and COL4AS, indispensable component of hyaline cartilage and basement membrane respectively, were significantly downregulated, as well as genes in WNT family, including WNT2, WNT11, and WNT16. In contrast, matrix metalloproteinase 13 （MMP13） was found to be significantly upregulated in RA patients. MMP13 is a matrix metallopeptidase that degrade extracellular matrix and hyaline cartilage, and it could possibly interact with other proteins to regulate morphogenesis. Conclusion Molecular mechanisms underlying RA pathogenesis were investigated by analyzing the public datasets. A few genes that associated with extracellular matrix degradation, construction and regulation, including MMP13, WNT2, WNT11, WNT16, COL9A3 and COL4AS, could be regarded as therapeutic targets in RA treatment.

关 键 词：关节炎 类风湿 膝关节 滑膜 成纤维细胞 基因表达谱 

分 类 号：R593.22[医药卫生—内科学]