基于生物信息学分析筛选骨关节炎差异表达基因
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摘要
目的基于生物信息学分析筛选骨关节炎相关的差异表达基因(DEGs),并分析其生物学功能。方法从GEO数据库下载微阵列数据集GSE1919,其包括5个骨关节炎样品和5个匹配的对照样品。利用R语言的Limma工具包进行数据分析,筛选DEGs。利用DAVID数据库对DEGs进行基因本体富集分析,利用京都基因与基因组百科全书数据库对上调DEGs进行信号通路分析。基于STRING数据库的信息识别蛋白质-蛋白质互相作用(PPI),使用Cytoscape软件3.4.0进行PPI网络构建。结果共获得1 145个DEGs,包括483个上调的DEGs和662个下调的DEGs。上调的DEGs主要涉及受体活性、细胞黏附分子活性,主要集中于细胞外组分、细胞膜、细胞外间隙等,主要与细胞通信、信号转导有关。上调的DEGs显著富集于肿瘤坏死因子、细胞黏附分子、丝裂原活化蛋白激酶、黏着斑、细胞因子受体相互作用以及磷脂酰肌醇-3-羟激酶-蛋白激酶B等信号通路。白细胞介素(IL)-6、IL-8、胰岛素样生长因子(IGF)和血管紧张素原(AGT)等基因为PPI网络的核心基因。结论 IL-6、IL-8、IGF和AGT基因可能是参与骨关节炎发展的重要基因。
Objective To screen the differentially expressed genes(DEGs) related to osteoarthritis,and to analyze the biological function of the DEGs.Methods The microarray dataset GSE1919 was downloaded from the GEO database,including 5 samples of osteoarthritis and 5 matched controlled samples.Data analysis was conducted using Limma package of R Language for screening DEGs.DAVID database was used for Gene Ontology enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes database for signaling pathway analysis of up-regulated DEGs.The protein-protein interaction(PPI) was distinguished according to the information of STRING database,the PPI network was established using Cytoscape software 3.4.0.Results A total of 1145 DEGs were obtained,including 483 up-regulated and 662 down-regulated DEGs.The up-regulated DEGs were mainly involved in receptor activity and cell adhesion molecule activity,commonly existed in extracellular component,cell membrane and extracellular space,and were related to intercellular communication and signal transduction mostly.The up-regulated DEGs were significantly enriched in the signaling pathways of tumor necrosis factor,cell adhesion molecule,mitogen-activated protein kinases,focal adhesion,interaction between cytokine receptors,phosphatidylinositol-3-kinase-protein kinase B,and ect.Interleukin(IL)-6,IL-8,insulin-like growth factor(IGF) and angiotensinogen(AGT) genes were the core genes of PPI network.Conclusion IL-6,IL-8,IGF and AGT genes may be the important genes involved in the development of osteoarthritis.
Objective To screen the differentially expressed genes(DEGs) related to osteoarthritis,and to analyze the biological function of the DEGs.Methods The microarray dataset GSE1919 was downloaded from the GEO database,including 5 samples of osteoarthritis and 5 matched controlled samples.Data analysis was conducted using Limma package of R Language for screening DEGs.DAVID database was used for Gene Ontology enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes database for signaling pathway analysis of up-regulated DEGs.The protein-protein interaction(PPI) was distinguished according to the information of STRING database,the PPI network was established using Cytoscape software 3.4.0.Results A total of 1145 DEGs were obtained,including 483 up-regulated and 662 down-regulated DEGs.The up-regulated DEGs were mainly involved in receptor activity and cell adhesion molecule activity,commonly existed in extracellular component,cell membrane and extracellular space,and were related to intercellular communication and signal transduction mostly.The up-regulated DEGs were significantly enriched in the signaling pathways of tumor necrosis factor,cell adhesion molecule,mitogen-activated protein kinases,focal adhesion,interaction between cytokine receptors,phosphatidylinositol-3-kinase-protein kinase B,and ect.Interleukin(IL)-6,IL-8,insulin-like growth factor(IGF) and angiotensinogen(AGT) genes were the core genes of PPI network.Conclusion IL-6,IL-8,IGF and AGT genes may be the important genes involved in the development of osteoarthritis.
引文
[1] Martel-Pelletier J,Barr AJ,Cicuttini FM,et al.Osteoarthritis[J].Nat Rev Dis Primers,2016,2:16 072.
[2] Hunter DJ,Schofield D,Callander E.The individual and socioeconomic impact of osteoarthritis[J].Nat Rev Rheumatol,2014,10(7):437-441.
[3] Scanzello CR,Goldring SR.The role of synovitis in osteoarthritis pathogenesis[J].Bone,2012,51(2):249-257.
[4] Kleine SA,Budsberg SC.Synovial membrane receptors as therapeutic targets:a review of receptor localization,structure,and function[J].J Orthop Res,2017,35(8):1 589-1 605.
[5] 尹崑,卫小春,丁娟,等.关节软骨损伤和滑膜炎关系的临床研究[J].中国药物与临床,2013,13(12):1 555-1 557.
[6] Mathiessen A,Conaghan PG.Synovitis in osteoarthritis:current understanding with therapeutic implications[J].Arthritis Res Ther,2017,19(1):18.
[7] Reynard LN,Loughlin J.Insights from human genetic studies into the pathways involved in osteoarthritis[J].Nat Rev Rheumatol,2013,9(10):573-583.
[8] Li M,Zhi L,Zhang Z,et al.Identification of potential target genes associated with the pathogenesis of osteoarthritis using microarray based analysis[J].Mol Med Rep,2017,16(3):2 799-2 806.
[9] Dong S,Xia T,Wang L,et al.Investigation of candidate genes for osteoarthritis based on gene expression profiles[J].Acta Orthop Traumatol Turc,2016,50(6):686-690.
[10] Ungethuem U,Haeupl T,Witt H,et al.Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis[J].Physiol Genomics,2010,42A(4):267-282.
[11] Xiao ZF,Su GY,Hou Y,et al.Cartilage degradation in osteoarthritis:a process of osteochondral remodeling resembles the endochondral ossification in growth plate?[J].Med Hypotheses,2018,121:183-187.
[12] Cram P,Lu X,Kates SL,et al.Total knee arthroplasty volume,utilization,and outcomes among Medicare beneficiaries,1991-2010[J].JAMA,2012,308(12):1 227-1 236.
[13] Ibi M.Inflammation and tissue remodeling as potential therapeutic targets[J].Biol Pharm Bull,2019,42:538-542.
[14] Webb GR,Westacott CI,Elson CJ.Chondrocyte tumor necrosis factor receptors and focal loss of cartilage in osteoarthritis[J].Osteoarthritis Cartilage,1997,5(6):427-437.
[15] Charlier E,Relic B,Deroyer C,et al.Insights on molecular mechanisms of chondrocytes death in osteoarthritis[J].Int J Mol Sci,2016,17(12).pii:E2146.
[16] Pigossi SC,Anovazzi G,Finoti LS,et al.Functionality of the interleukin 8 haplotypes in lymphocytes and macrophages in response to gram-negative periodontopathogens[J].Gene,2019,689:152-160.
[17] Franckhauser S,Elias I,Rotter Sopasakis V,et al.Overexpression of Il6 leads to hyperinsulinaemia,liver inflammation and reduced body weight in mice[J].Diabetologia,2008,51(7):1 306-1 316.
[18] Bernstein KE,Giani JF,Shen XZ,et al.Renal angiotensin-converting enzyme and blood pressure control[J].Curr Opin Nephrol Hypertens,2014,23(2):106-112.
[19] Tsukamoto I,Akagi M,Inoue S,et al.Expressions of local renin-angiotensin system components in chondrocytes[J].Eur J Histochem,2014,58(2):2 387.
[20] Flammer AJ,Sudano I,Hermann F,et al.Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis[J].Circulation,2008,117(17):2 262-2 269.
[21] Ni Q,Tan Y,Zhang X,et al.Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway[J].Sci Rep,2015,5:14 711.
[2] Hunter DJ,Schofield D,Callander E.The individual and socioeconomic impact of osteoarthritis[J].Nat Rev Rheumatol,2014,10(7):437-441.
[3] Scanzello CR,Goldring SR.The role of synovitis in osteoarthritis pathogenesis[J].Bone,2012,51(2):249-257.
[4] Kleine SA,Budsberg SC.Synovial membrane receptors as therapeutic targets:a review of receptor localization,structure,and function[J].J Orthop Res,2017,35(8):1 589-1 605.
[5] 尹崑,卫小春,丁娟,等.关节软骨损伤和滑膜炎关系的临床研究[J].中国药物与临床,2013,13(12):1 555-1 557.
[6] Mathiessen A,Conaghan PG.Synovitis in osteoarthritis:current understanding with therapeutic implications[J].Arthritis Res Ther,2017,19(1):18.
[7] Reynard LN,Loughlin J.Insights from human genetic studies into the pathways involved in osteoarthritis[J].Nat Rev Rheumatol,2013,9(10):573-583.
[8] Li M,Zhi L,Zhang Z,et al.Identification of potential target genes associated with the pathogenesis of osteoarthritis using microarray based analysis[J].Mol Med Rep,2017,16(3):2 799-2 806.
[9] Dong S,Xia T,Wang L,et al.Investigation of candidate genes for osteoarthritis based on gene expression profiles[J].Acta Orthop Traumatol Turc,2016,50(6):686-690.
[10] Ungethuem U,Haeupl T,Witt H,et al.Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis[J].Physiol Genomics,2010,42A(4):267-282.
[11] Xiao ZF,Su GY,Hou Y,et al.Cartilage degradation in osteoarthritis:a process of osteochondral remodeling resembles the endochondral ossification in growth plate?[J].Med Hypotheses,2018,121:183-187.
[12] Cram P,Lu X,Kates SL,et al.Total knee arthroplasty volume,utilization,and outcomes among Medicare beneficiaries,1991-2010[J].JAMA,2012,308(12):1 227-1 236.
[13] Ibi M.Inflammation and tissue remodeling as potential therapeutic targets[J].Biol Pharm Bull,2019,42:538-542.
[14] Webb GR,Westacott CI,Elson CJ.Chondrocyte tumor necrosis factor receptors and focal loss of cartilage in osteoarthritis[J].Osteoarthritis Cartilage,1997,5(6):427-437.
[15] Charlier E,Relic B,Deroyer C,et al.Insights on molecular mechanisms of chondrocytes death in osteoarthritis[J].Int J Mol Sci,2016,17(12).pii:E2146.
[16] Pigossi SC,Anovazzi G,Finoti LS,et al.Functionality of the interleukin 8 haplotypes in lymphocytes and macrophages in response to gram-negative periodontopathogens[J].Gene,2019,689:152-160.
[17] Franckhauser S,Elias I,Rotter Sopasakis V,et al.Overexpression of Il6 leads to hyperinsulinaemia,liver inflammation and reduced body weight in mice[J].Diabetologia,2008,51(7):1 306-1 316.
[18] Bernstein KE,Giani JF,Shen XZ,et al.Renal angiotensin-converting enzyme and blood pressure control[J].Curr Opin Nephrol Hypertens,2014,23(2):106-112.
[19] Tsukamoto I,Akagi M,Inoue S,et al.Expressions of local renin-angiotensin system components in chondrocytes[J].Eur J Histochem,2014,58(2):2 387.
[20] Flammer AJ,Sudano I,Hermann F,et al.Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis[J].Circulation,2008,117(17):2 262-2 269.
[21] Ni Q,Tan Y,Zhang X,et al.Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway[J].Sci Rep,2015,5:14 711.