常染色体显性遗传多囊肾差异表达基因的研究  

Differential gene expression pattern between autosomal dominant polycystic kidney tissue and normal kidney tissue: a DNA microarray study

作　　者：崔心刚[1] 王立明[1] 朱有华[1] 

机构地区：[1]第二军医大学长征医院全军器官移植研究所,上海200003

出　　处：《第二军医大学学报》2006年第2期182-185,共4页Academic Journal of Second Military Medical University

摘　　要：目的:应用表达谱芯片研究常染色体显性遗传多囊肾病(ADPKD)与正常肾组织基因表达的差异,探讨此病的致病因素及可能的治疗途径。方法:等量的人正常肾和ADPKD肾组织的mRNA分别用Cy3和Cy5逆转录荧光标记,制作cDNA探针,混合后与4 096点人cDNA表达谱芯片进行杂交,ScanArray4000扫描仪扫描芯片荧光信号图像,数字化处理和分析后比较两种组织基因表达谱的差异。RT-PCR法验证其中4条基因表达水平。结果:在ADPKD肾组织与正常肾组织中存在463条差异表达基因,其中206条基因在多囊肾组织中高表达,特别是细胞周期素D2(cyclin D2)、基质金属蛋白酶1(MMP1)、组织金属蛋白酶抑制因子1(TIMP1)、成纤维细胞活化蛋白基因等;257条基因在多囊肾组织中低表达,特别是蛋白磷酸酶1A、酸性磷酸酶1基因等。RT-PCR法验证的4条基因表达水平与芯片结果相一致。结论:ADPKD病理改变可能与细胞周期蛋白、MMPs以及各种生长因子相关基因的上调有关,钙调素抑制剂和MMPs抑制剂可能会对其有一定的治疗作用。Objective：To study the differential gene expression pattern between autosomal dominant polycystic and normal kidney tissue, and to deduce the etiological factor and treatment for autosomal dominant polycystic kidney disease（ADPKD）. Methods： The cDNA probes were prepared by labelling normal kidney tissue mRNA and ADPKD tissue mRNA with Cy3-dUTP and Cy5-dUTP separately through reverse transcription. The probes were then hybridized with the DNA microarrays （PCR products of 4 096 human cDNAs onto specially treated glass slides） and the fluorescent signals were scanned with ScanArray 4000 scanner. Semi-quantitive RT-PCR was performed to test the expression level of 4 related genes. Results： Of the 4 096 genes screened,463 genes showed obvious changes. Expression of 206 genes was upregulated in the polycystic kidney tissue,especially cyclin D2, MMPs, TIMP1 and fibroblast activation protein; expression of 257 genes was downregulated, especially phosphatase 1A and acid phosphatase 1. The expression of genes tested by RT-PCR was in accordance with those detected by cDNA microarray. Conclusion： ADPKD may be related to the upregulation of cyclin,MMPs,and various kinds of growth factors, and drugs like inhibitors of CaM and MMPs might have therapeutical effects on ADPKD. EKEY WORDS3 polycystic kidney,autosomal dominant; kidney; gene expression profiling

关 键 词：多囊肾 常染色体显性 基因表达谱 成纤维细胞 钙调素抑制剂 

分 类 号：R692[医药卫生—泌尿科学]