Title基于文献挖掘的增生性瘢痕相关基因的生物信息学分析
Other TitlesLiterature mining and bioinformatic analysis of dysregulated genes in hypertrophic scar
Authors黄琛
李博仑
秦泽莲
Affiliation100191北京,北京大学第三医院成形外科
100191北京,北京大学第三医院中心实验室
北京大学第三医院成形外科,北京,100191
Keywords计算生物学 瘢痕,肥大性 皮肤 Computational biology Cicatrix,hypertrophic Skin
Issue Date2011
Publisher中华整形外科杂志
Citation中华整形外科杂志.2011,27,(6),453-460.
Abstract目的 比较增生性瘢痕(hypertrophic scar,HS)与正常皮肤的基因表达差异,从分子水平揭示HS的发病机制,为其临床防治提供新思路.方法 利用PubMed公共数据库文献挖掘HS与正常皮肤的差异表达基因,确定HS相关基因,并进行蛋白-蛋白相互作用网络、生物学通路、GeneOntology(基因本体)和功能注释聚类等生物信息学分析.结果 筛选HS相关基因55个(上调基因46个,下调基因9个).51个基因构成蛋白-蛋白相互作用网络,其中上调基因TGFB1、FN1、JUN、COL1A1、CTGF、VEGFA、FOS、COL3A1、IGF1、IL4、PELO、SMAD2、TIMP1、PCNA、ITGA4和下调基因ITGB1和DCN为此网络中心节点.HS相关基因参与黏着斑形成、整合素信号转导和肿瘤相关等生物学通路.并在细胞表面受体介导和胞内信号转导、组织发育与形态发生、细胞凋亡与增殖、大分子合成与代谢等生物过程,钙离子结合、双链DNA结合、启动子结合、肝素结合和促分裂素原活化蛋白激酶(MAPK)激活等分子功能中起着重要作用.功能注释聚类显示,HS相关基因多与表皮组织发育,血管生成,以及细胞凋亡调控有关.结论 TGFB1、FN1、JUN等关键基因,以及表皮组织发育,血管生成,以及细胞外基质-整合素-黏着斑相关的生物学通路、生物学过程和分子功能在HS的发生发展中可能起着重要作用,对其进一步分析有利于揭示HS的发病机制,并为临床治疗提供新的靶点.
To explore the pathogenesis mechanism of hypertrophic scar (HS) and the effective means for its clinical treatment, the difference of the gene expressions between HS and normal skin was compared.The differentially expressed genes between HS and normal skin were obtained by mining PubMed. The dysregulated genes in HS were analyzed by a series of bioinformatics methods, including protein-protein interaction networks, pathways, Gene Ontology and functional annotation clustering analysis.A total of 55 dysregulated genes in HS was identified (46 up-regulated genes and 9 down-regulated genes). Fifty-one genes were found to encode proteins with interaction network, including up-regulated genes TGFB1, FN1, JUN, COL1A1, CTGF, VEGFA, FOS, COL3A1, IGF1, IL4, PELO, SMAD2, TIMP1, PCNA, and ITGA4 and down-regulated genes ITGB1 and DCN as the central nodes for this network. The dysregulated genes in HS involved in a variety of biological pathways, such as focal adhesion formation, integrin signal transduction, and tumor formation. Furthermore, the dysregulated genes in HS played the important roles in biological processes of cell surface receptor linked signal transduction, tissue development, cell proliferation and apoptosis, and macromolecule biosynthetic process, as well as in molecular function of calcium ion binding, double-stranded DNA binding, heparin binding, promoter binding and MAP kinase activity. The results of functional annotation clustering analysis revealed that the dysregulated genes in HS involved in epidermis development, angiogenesis, and apoptosis.Such key genes as TGFB1, FN1, and JUN, along with the pathways, biological processes and molecular functions involving epidermis development, angiogenesis, and extracellular matrix-integrin-focal adhesion signal transduction may play the important roles in the development of HS. The investigations of the dysregulated genes in HS could provide the new targets for clinical treatment.
URIhttp://hdl.handle.net/20.500.11897/191683
ISSN1009-4598
DOI10.3760/cma.j.issn.1009-4598.2011.06.013
IndexedPubMed
中文核心期刊要目总览(PKU)
中国科技核心期刊(ISTIC)
中国科学引文数据库(CSCD)
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