CTGF抗体对糖尿病肾病小鼠肾小球β-catenin及足细胞上皮间充质转化的影响

Effects of CTGF antibody on glomerular β-catenin expression and podocyte epithelialmesenchymal transition in mice with diabetic nephropathy

目的:探讨结缔组织生长因子(connective tissue growth factor,CTGF)抗体对糖尿病肾病小鼠肾小球β-catenin表达及足细胞上皮间充质转化的影响。方法 :C57BL/6J小鼠随机分为3组:对照组、糖尿病肾病模型组和CTGF抗体干预组,观察尿白蛋白排泄率、肾质量指数、肾脏病理改变、肾小球β-catenin mRNA和蛋白表达以及CTGF抗体对其表达水平及足细胞上皮间充质转化的影响。结果:与对照组相比,模型组小鼠尿蛋白增多,肾小球系膜基质增生,肾小球β-catenin mRNA和蛋白表达水平增加,足细胞上皮细胞标志物nephrin下调,而间充质细胞标志物desmin上调;CTGF抗体可抑制肾小球β-catenin表达上调和足细胞上皮间充质转化,减轻蛋白尿和肾小球系膜基质增生。结论 :阻断CTGF可抑制糖尿病肾病小鼠肾小球β-catenin表达上调及足细胞上皮间充质转化改变,减轻足细胞损伤。

Objective： To investigate effects of connective tissue growth factor（CTGF） antibody on glomerular β-catenin expression and podocyte injury in mice with diabetic nephropathy. Methods： C57BL/6J mice were randomly divided into three groups as follows： control group, diabetic nephropathy model group and CTGF antibody treatment group. The urinary albumin excretion, kidney weight index,renal pathological changes and the expression of β-catenin in glomeruli were analyzed. In addition, the effects of CTGF antibody on β-catenin expression and podocyte epithelial-mesenchymal transition were studied. Results： Compared with control group, the mice with diabetic nephropathy showed more urinary albumin excretion and mesangial metrix proliferation, the mRNA and protein expression of β-catenin in glomeruli were increased, and the downregulation of nephrin and upregulation of desmin in podocyte were also observed. Furthermore, blocking CTGF by specific antibody prevented the β-catenin overexpression and diminished podocyte epithelial-mesenchymal transition in diabetic nephropathy mice. Conclusion： CTGF antibody can protect podocytes from injury in diabetic nephropathy mice by reducing β-catenin overexpression and preventing epithelial-mesenchymal transition.