小鼠单侧输尿管梗阻诱导肾脏纤维化模型中Cadherin6的表达变化  

Expression of cadherin6 in renal fibrosis of mice with unilateral ureteral obstruction

作　　者：梁蝶霏 常瑞明[2] 宋自姣 梁蔚文[3] 刘珊英[3] 严励[1] 李焱[1] LIANG Diefei;CHANG Ruiming;SONG Zijiao;LIANG Weiwen;LIU Shanying;YAN Li;LI Yan(Department of Endocrinology ,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Boji Medical Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院内分泌科,广州510120 [2]中山大学孙逸仙纪念医院博济医疗中心,广州510120 [3]中山大学孙逸仙纪念医院广东省恶性肿瘤表观遗传和基因调控重点实验室,广州510120

出　　处：《岭南现代临床外科》2018年第1期9-13,共5页Lingnan Modern Clinics in Surgery

基　　金：国家自然科学基金(81370847);默克雪兰诺糖尿病研究基金

摘　　要：目的研究钙黏蛋白6(cadherin6,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-q PCR检测肾组织FSP-1、TGF-β1、CDH6 m RNA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-q PCR及Western Blot分别检测FN1、PAI-1、CDH6 m RNA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 m RNA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-1m RNA表达水平上调,CDH6 m RNA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。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 day21after operation.Hematoxylin and eosin(HE)staining was used for histopathologic examination.RT-qPCR was used to evaluate mRNA level of FSP?1,TGF-β1and CDH6.Immunohistochemistry was used to measure protein level of FSP-1and CDH6.HK-2human 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,CDH6or protein level of CDH6respectively.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,CDH6were up-regulated in obstructed kidneys while compared with sham-operated kidneys.Furthermore,immunohistochemistry showed that FSP-1and CDH6were lowly expressed in sham?operated kidneys while they were higher in obstructed ones.TGF-β1facilitated the transition of HK-2cells into morphology of fibroblast-like cells,up-regulating mRNA level of FN1,PAI-1,CDH6and protein level of CDH6in HK-2cells.Conclusion Expression of cadherin6and fibrosis?related biomarkers were upregulated in HK-2cells induced by TGF-β1,accompanied with phenotype transition into mesenchymal cells.This may contribute to renal fibrosis induced by unilateral ureteral obstruction.

关 键 词：TGF-Β1 钙黏蛋白6 单侧输尿管梗阻 肾脏纤维化 

分 类 号：R692.9[医药卫生—泌尿科学] R693.2[医药卫生—外科学]