应用PCR芯片筛查人重度肾积水组织的纤维化相关基因  

PCR-microarray analysis of fibrosis-associate gene expression in extensive fibrotic renal tissue resulting from hydronephrosis

作　　者：姚颐[1] 张杰[2] 叶达夫[1] 谭大清[1] 彭建平[1] 

机构地区：[1]武汉大学人民医院泌尿外科,湖北430060 [2]武汉大学生命科学院病毒学国家重点实验室,湖北430070

出　　处：《国际外科学杂志》2009年第7期445-448,共4页International Journal of Surgery

基　　金：高等学校博士学科点专项科研基金资助项目（No.20060486054）,武汉大学生命科学院病毒学国家重点实验室

摘　　要：目的探讨纤维化相关基因，特别是与转化生长因子β（transforming growth factor-β，TGF-β）信号通路相关的基因在人重度积水肾与正常肾组织中的差异表达变化。方法收集临床重度肾积水新鲜标本12例，正常肾组织标本6例，分别提取总RNA并纯化。选择TGF-β／骨形成蛋白（bone morphogenetic protein，BMP）信号通路PCR-芯片，采用比较阈值法（△△Ct法）分析比较两组基因的差异表达。以表达差异（即上调或下调）大于2倍的基因为有意义的差异基因。结果共筛查出表达具有显著性差异的基因49个，包括TGF-β超家族成员基因及其受体、TGF-β信号通路靶分子和相关调控分子等等。其中上调25个，包括BMP3、Ⅰ型胶原仅1链（Col-Ⅰ α1）、Nodal、GSC、胰岛素样生长因子1（insulin—like growth factor 1，IGF1）等；下调24个，包括Lefty 1（left—right determination factor1）、BMP7、BMP2和骨形成蛋白内皮结合调节因子（BMP binding endothelial regulator，BMPER）等。结论证明了Nodal、GSC和IGF1等是促进肾纤维化改变的重要因子，并推测Lefry1与BMP家族的部分成员，包括BMP2—3、BMP7和BMPER等，在调控终末期肾积水纤维化改变中占有重要地位。Objective To investigate the fibrosis-associated genes, especially those transforming growth factor-β（TGF-β） associated, expression in the tissue of extensive fibrotic kidney resulting from severe hydronephrosis. Methods Compared 12 extensive fibrotic kidneys resulting from severe hydronephrosis with 6 normal renal tissues using PCR array. All samples were collected from our hospital from Aug. 2005 to Dec. 2006. The data were treated with AACt method. When 2^△△Ct≤0.5 or≥2, the difference was considered significant. Results A total of 49 differential genes expressed in the fibrotic renal tissues were screened out, of which, 25 were up-regulated and 24 were down-regulated. The differential genes included members and receptors of TGF-β super family and bone morphogenetic protein（BMP） family, target molecule of TGF-β or BMP signal pathway and several regulators. Conclusions Through investigating with PCR array, we certificated the positive effect of Nodal, GSC and IGF1 to renal fibrosis. And we suppose that TGF-β play a secondary role in renal fibrosis, while BMP family and Leftyl work in a functional genome in the regulating of renal fibrosis.

关 键 词：肾积水 肾纤维化 基因芯片 功能基因组学 

分 类 号：R692.2[医药卫生—泌尿科学] R450[医药卫生—外科学]