Abstract: ［Abstract］ Objective To investigate the expression of cadherin6 （CDH6） in renal fibrosis. Methods Mice were subjected to unilateral ureteral obstruction（UUO）and kidneys were harvested at day 21 after operation. Hematoxylin and eosin （HE）staining was used for histopathologic examination. RT?qPCR was used to evaluate mRNA level of FSP?1, TGF?β1 and CDH6. Immunohistochemistry was used to measure protein level of FSP?1 and CDH6. HK?2 human renal proximal tubule epithelial cells were stimulated with TGF?β1. RT?qPCR or Western Blot was used to evaluate mRNA of FSP?1, TGF?β1, CDH6 or protein level of CDH6 respectively. Results Compared with Sham group, HE staining showed renal tubular atrophy and deposition of extracellular matrix in UUO group. mRNA levels of FSP?1, TGF?β1, CDH6 were up?regulated in obstructed kidneys while compared with sham?operated kidneys. Furthermore, immunohistochemistry showed that FSP?1 and CDH6 were lowly expressed in sham?operated kidneys while they were higher in obstructed ones. TGF?β1 facilitated the transition of HK?2 cells into morphology of fibroblast?like cells, up?regulating mRNA level of FN1, PAI?1, CDH6 and protein level of CDH6 in HK?2 cells. Conclusion Expression of cadherin6 and fibrosis?related biomarkers were upregulated in HK?2 cells induced by TGF?β1, accompanied with phenotype transition into mesenchymal cells. This may contribute to renal fibrosis induced by unilateral ureteral obstruction.

Key words: cadherin6, unilateral ureteral obstruction, renal fibrosis, TGF?β1

摘要： ［摘要］目的 研究钙黏蛋白6（cadherin 6，CDH6）在肾脏纤维化中表达的变化。方法 建立单侧输尿管梗阻（UUO）小鼠模型，术后21天收获肾脏组织，HE染色观察肾间质纤维化程度，RT?qPCR检测肾组织FSP?1、TGF?β1、CDH6mRNA表达量，免疫组化染色检测肾组织FSP?1、CDH6蛋白表达量；TGF?β1刺激人肾小管上皮细胞HK?2，RT?qPCR及WesternBlot分别检测FN1、PAI?1、CDH6 mRNA表达量及CDH6蛋白表达量。结果 HE染色显示UUO组小鼠肾脏出现肾小管萎缩、大量基质沉积，与Sham组相比，UUO组小鼠肾脏组织FSP?1、TGF?β1、CDH6 mRNA表达量及FSP?1、CDH6蛋白表达量均上调；细胞实验结果显示，与空白对照组相比，TGF?β1诱导的HK?2细胞形态向成纤维细胞转变，FN1、PAI?1mRNA表达水平上调，CDH6 mRNA及蛋白表达水平上调。结论 TGF?β1诱导的肾小管上皮细胞CDH6及纤维化相关因子表达上调，伴随上皮细胞向间质表型转化，可能参与单侧输尿管梗阻诱导的小鼠肾脏纤维化的发展。

关键词: 肾脏纤维化, 钙黏蛋白6, TGF?β1, 单侧输尿管梗阻