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1、瘢痕疙瘩成纤维细胞的基因组学研究中华整形外科杂志2005年7月第2鲞箜塑型垡!』!:!:!瘢痕疙瘩成纤维细胞的基因组学研究王春梅百束比古张启旭严笠中泽南堂【摘要】目的寻找瘢痕疙瘩致病相关基因,探讨瘢痕疙瘩的发生机理.方法利用含1100个人类肿瘤相关基因的cDNA芯片(cDNA—microarray)对耳垂和胸部瘢痕疙瘩及正常皮肤成纤维细胞进行检测,初步分析瘢痕疙瘩成纤维细胞与正常皮肤成纤维细胞基因总体表达的差异,并筛选出差异基因.结果在耳垂及胸部瘢痕疙瘩成纤维细胞中,分别有8种和l7种特异性表达基因被
2、检出.在正常皮肤中特异性表达的细胞增殖抑制基因Mda一7,在耳垂及胸部瘢痕疙瘩成纤维细胞中均未被表达.结论多种基因参与了瘢痕疙瘩的形成过程,瘢痕疙瘩成纤维细胞与正常皮肤成纤维细胞之间存在基因表达的差异,增殖因子受体PAR一1和增殖抑制基因Mda一7可能参与瘢痕疙瘩的形成.【关键词】瘢痕疙瘩成纤维细胞基因组学基因芯片基因PathologicalgenomicsofkeloidfibroblasticceHsWANGChun-mei,HikoHyakusok,ZHANGQi-xu,YANLi,NandoN
3、akazawa..PlasticSurgeryHospiml,ChineseAcademyofMedicalSciences,Bei.jing100041,China【Abstract】ObjectiveKeloidsresultfromtheabnormalrepairofthetissuesafterskininjurieswherethepathologicalovergrowthoflargeandactivefibroblasticcellsexpandsbeyondtheboundarie
4、softheinitiatingwound.Imbalancedexpressionofgeneswithanasyetunknownregulatorymechanismseemstoresultinthehypertrophicdevelopmentoffibroblasticcellsandover—productionsofcollagen.Togetinformationastogeneswhichfunctionintheactivelygrowingkeloidfibroblasts,w
5、ehaveappliedageneexpressionDNA—microarraytechniquebyanalyzingbroadrangeofgenesatonceinasystematicfashion.MethodsDifferentialgeneexpressionsofkeloidfibroblasticcelllinesagainstanormalskinfibroblasticcellline,allofthecelllineshadbeenpropagatedinourlab,wer
6、eanalyzedusingacDNA—microarraytechnique.mRNAwasextractedfromthecontrolnormalskincellsandthetwolinesofkeloidfibroblasticcells,onefromear-lobekeloidtissueandtheotherfromchestkeloidtissue,wassubjectedtoaDNAmicroarrayanalysiswhichincludes1100humangenes(TaKa
7、RaIntelliGeneHumanCHIPlKSetI).Results8geneswerefoundtobeexpressedexclusivelyinear—lobekeloidfibroblasticceillines.Ceilsfromchestkeloidweredetectedtoexpress17genes,specifically.CoagulationfactorII(thrombin)receptorgene,KIAA0367proteingene,andmatrilin一2ge
8、newerefoundtobethemostcommonlyexpressedgenesinthekeloidcells.Suppressorgenes,likemelanomadifferentiationassociatedgene一7,Mda一7(U16261),wereexpressedinnormalskinfibroblastsbutwerenotexpressedinkeloidfibroblastsmaybeimplicatedinthe