增生性瘢痕与正常皮肤组织差异表达基因的筛选与生物信息学分析  

Screening and bioinformatics analysis of differentially expressed genes in hyperplastic scar

作　　者：胡洋红[1,2,3] 胡杨柳[4] 刘德伍[1] 俞建兴[5] 刘德明[6] 

机构地区：[1]南昌大学第一附属医院烧伤研究所,江西南昌330006 [2]南昌大学 [3]江西中医药大学,江西南昌330006 [4]江西护理职业技术学院,江西南昌330052 [5]中山大学附属第一医院特诊激光医学整形美容中心,广东广州510080 [6]南昌大学医学院解剖学教研室,江西南昌330006

出　　处：《南方医科大学学报》2014年第7期939-944,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(81060323)~~

摘　　要：目的比较人增生性瘢痕与正常皮肤组织中mRNA表达谱的差异,并对差异基因行生物信息分析,从分子水平全面探讨增生性瘢痕的发病机制,为临床治疗提供新靶点。方法收集我院手术切除增生性瘢痕及其邻近正常皮肤组织各3例,采用Trizol试剂提取总RNA,进行mRNA芯片检验,利用Genespring 10.0软件筛选表达差异基因,并对增生性瘢痕和正常皮肤组间组内行聚类分析,应用DAVID Bioinformatics Resources 6.7对差异基因进行基因本体(GO)、生物学通路(Pathway)分析,获得差异基因相关功能的功能富集类。结果人增生性瘢痕与正常皮肤组织相比较,3例样品重复一次相对表达量比值在2倍以上变化的mRNA有6126条,2倍以上上调的mRNA共3142条,2倍以上下调的mRNA共2984条,5倍以上上调的mRNA共28条,5倍以上下调的mRNA共44条;重复两次相对表达量比值在2倍以上变化的mRNA有6042条,2倍以上上调的mRNA共3004条,2倍以上下调的mRNA共3038条,5倍以上上调的mRNA共25条,5倍以上下调的mRNA共38条;其中3例样品都上调的mRNA有3832条,2倍以上上调的1920条,2倍以上下调的1912条,5倍以上上调的18条,5倍以上下调29条。CDKN1C,CDKN2A,CTNNA3,COL6A3,HOXB4等差异表达基因与细胞周期、细胞增殖、以及细胞粘附等生物学过程密切相关,TGFβ1,CDKN1C,CDKN2A,CDC14A,ITGB6,EGF等差异表达基因主要参与黏着斑形成、b转化因子信号通路、细胞周期信号通路、P53信号通路、肿瘤相关信号通路。结论人增生性瘢痕与正常皮肤组织比较,mRNA表达谱发生了明显变化,TGFβ1,SMAD2,SMAD7,BAX,IGF,COL1A1,COL1A2,MMPs,CDC14A,ITGB6,EGF,CDKN1C,CDKN2A,CTNNA3,HOXA3等相关基因参与的生物过程、分子功能、信号通路可能与增生性瘢痕的发生发展密切相关。Objective To screen differentially expressed genes in hyperplastic scar to explore the pathogenesis of hyperplastic scar and identify new therapeutic targets. Methods Three pairs of surgical specimens of hyperplastic scar and adjacent normal skin tissues were collected to investigate the differentially expressed genes in hyperplastic scar using Agilent gene oligonucletide microarray and clustering analysis. DAVID Bioinformatics Resources6.7 was used for GO analysis and pathway analysis. Results and Conlcusion Distinctly different gene expression profiles were found between hyperplastic scar tissues and normal skin tissues. Compared with normal skin tissue, hyperplastic scar tissues showed 3142 up-regulated and 2984 down-regulated genes by two folds and 28 up-regulated and 44 down-regulated genes by 5 folds after repeating the experiment once; after repeating the experiment twice, 3004 genes were found up-regulated and 3038 down-regulated by 2 folds and 25 up-regulated and 38 down-regulated by 5 folds in hyperplastic scars. In all the 3 specimens, 1920 genes were up-regulated and 1912 down-regulated by 2 folds and 18 up-regulated and 29 down-regulated by 5 folds. The dysregulated genes in hyperplastic scar were involved in cell cycles, cell proliferation, immune response and cell adhesion （CDKN1C, CDKN2A, CTNNA3, COL6A3, and HOXB4） and in signaling pathway of focal adhesion, TGF-beta signaling pathway, p53 signaling pathway, cell cycle, and tumor-associated pathways （TGFβ1, CDKN1C, CDKN2A, CDC14A , ITGB6, and EGF）.

关 键 词：增生性瘢痕 基因 芯片 生物信息 

分 类 号：R622[医药卫生—整形外科]