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基于生物信息学分析骨关节炎中软骨生成祖细胞损伤的差异基因及中药预测
梁 爽,郭 赛,葛殊伟
0
(湖南中医药大学,湖南 长沙,410208)
摘要:
目的:通过生物信息学方法分析骨关节炎(OA)中软骨生成祖细胞(CPC)损伤的差异基因表达,并找出关键基因来预测可用于诊断或治疗CPC损伤的生物标志物及中药。方法:从GEO数据库下载CPC数据。共包含样本8 例。以R语言处理数据,得到差异表达基因。再使用DAVID数据库对差异表达基因进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。对显著差异表达的前100个差异表达基因进行分析后绘制蛋白质-蛋白质相互作用(PPI)网络图。比较关键基因在OA组织及正常组织中的表达水平。筛选网络中显著模块及关键基因,最后预测作用于关键基因的中药。结果:共筛选出DEGs 1027个,其中上调基因327个,下调基因700个。DEGs 显著富集于细胞外基质(ECM)受体相互作用、金黄色葡萄球菌感染、粘着斑、人乳头瘤病毒感染、磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)信号通路、肺结核等通路。前7个关键基因为:基质金属肽酶3(MMP3)、脂多糖结合蛋白(LBP)、基质金属肽酶1(MMP1)、脂质运载蛋白(LCN2)、人血浆丝氨酸蛋白激酶(SERPINA5)、成纤维细胞生长因子23(FGF23)、颗粒酶B(GZMB)。其中MMP3和LBP为核心基因。MMP3和LBP出现显著表达,预测出治疗CPC损伤的潜在代表中药有黄芩、淫羊藿、桃仁等。结论:MMP3和LBP的显著表达有助于区分OA中的CPC,并且有望成为诊断和治疗CPC损伤的生物标志物。
关键词:  骨关节炎  软骨生成祖细胞损伤  关键基因  生物信息学  中药预测
DOI:
Differentially expressed genes for chondrogenic progenitor cell in osteoarthritis based on bioinformatics and prediction of traditional Chinese medicine for treatment
LIANG Shuang,GUO Sai,GE Shuwei
(Hunan University of Chinese Medicine,Changsha 410208,Hunan,China)
Abstract:
Objective:To investigate the differentially expressed genes for chondrogenic progenitor cell (CPC) injury in osteoarthritis (OA) based on bioinformatics,and to identify the key genes for predicting the biomarkers for the diagnosis of CPC injury and the traditional Chinese medicine (TCM) drugs for treatment.Methods:CPC data were downloaded from GEO database,which contained 8 samples.R language was used for data processing to obtain the differentially expressed genes (DEGs).DAVID database was used to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs,and a protein-protein interaction network was constructed for the top 100 DEGs after analysis.The expression levels of key genes were compared between OA tissue and normal tissue.Significant modules and key genes were screened out from the network,and finally TCM drugs targeting the key genes were predicted.Results:A total of 1027 DEGs were screened out,among which 327 were upregulated and 700 were downregulated.DEGs were significantly enriched in the pathways such as extracellular matrix-receptor interaction,Staphylococcus aureus infection,adhesion plaque,human papillomavirus infection,the PI3K-Akt signaling pathway,and pulmonary tuberculosis.The top 7 key genes were matrix metalloproteinase 3 (MMP3),lipopolysaccharide-binding protein (LBP),matrix metalloproteinase 1 (MMP1),lipocalin-2 (LCN2),SERPINA5,fibroblast growth factor 23 (FGF23),and granzyme B (GZMB),among which MMP3 and LBP were core genes.When MMP3 and LBP showed significant expression,it was predicted that Scutellaria baicalensis,Herba Epimedii,and peach seed were potential representative TCM drugs for the treatment of CPC injury.Conclusion:The significant expression of MMP3 and LBP may help to differentiate CPC in OA,and therefore,they are expected to become the biomarkers for the diagnosis and treatment of CPC injury.
Key words:  osteoarthritis  chondrogenic progenitor cell injury  key gene  bioinformatics  prediction of traditional Chinese medicine

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