CAJ | 학술논문

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α1链(Col-Ⅰα1)、Nodal、GSC、胰岛素样生长因子1(insulin-like growth factor 1,IGFl)等;下调24个,包括Lefty l(left-right determination factor1)、BMP 7、BMP 2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IGFI等是促进肾纤维化改变的重要因子,并推测Leftyl与BMP家族的部分成员,包括BMP2～3、BMF7和BMPER等,在调控终末期肾积水纤维化改变中占有重要地位.
목적 탐토섬유화상관기인,특별시여전화생장인자β(transforming growth factor-β,TGF-β)신호통로상관적기인재인중도적수신여정상신조직중적차이표체변화.방법 수집림상중도신적수신선표본12례,정상신조직표본6례,분별제취총RNA병순화.선택TGF-β/골형성단백(bone morphogenetic protein,BMP)신호통로PCR-심편,채용비교역치법(△△Ct법)분석비교량조기인적차이표체.이표체차이(즉상조혹하조)대우2배적기인위유의의적차이기인.결과 공사사출표체구유현저성차이적기인49개,포괄TGF-β초가족성원기인급기수체、TGF-β신호통로파분자화상관조공분자등등.기중상조25개,포괄BMP3、Ⅰ형효원α1련(Col-Ⅰα1)、Nodal、GSC、이도소양생장인자1(insulin-like growth factor 1,IGFl)등;하조24개,포괄Lefty l(left-right determination factor1)、BMP 7、BMP 2화골형성단백내피결합조절인자(BMP binding endothelial regulator,BMPER)등.결론 증명료Nodal、GSC화IGFI등시촉진신섬유화개변적중요인자,병추측Leftyl여BMP가족적부분성원,포괄BMP2～3、BMF7화BMPER등,재조공종말기신적수섬유화개변중점유중요지위.
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 by-dronephrosis. 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 △△Ct method. When 2△△Ct≤<0.5 or≥2, the difference was considered sig-nificant. 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 certifi-cated the positive effect of Nodal, GSC and IGFI to renal fibrosis. And we suppose that TGF-β play a sec-ondary role in renal fibrosis, while BMP family and Leftyl work in a functional genome in the regulating of renal fibrosis.