狼疮性肾炎患者YAP1过表达与肾功能障碍相关

Ying Xie, Yuanyuan Ruan, Huimei Zou, Yixin Wang, Xin Wu, Xiaoying Li, Jiao Lai, Mingjun Shi, Ying Xiao, Yuanyuan Wang, Yuxia Zhou, Bing Guo, Fan Zhang
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引用次数: 2

摘要

目的:本研究的目的是测定狼疮性肾炎(LN)小鼠肾组织中yes相关蛋白1 (YAP1)的表达并阐明其在肾纤维化进展中的作用。方法:选择C57BL/6小鼠和MRL/lpr小鼠进行实验比较。取小鼠肾组织切片进行苏木精和伊红染色、马氏毛状体染色、天狼星染色和免疫组化。检测小鼠肾组织中YAP1 mRNA和蛋白水平,并分析YAP1与纤连蛋白(FN) mRNA水平的相关性。体外实验采用小鼠肾上皮细胞。细胞转染刺激后分为C57BL/6血清组(1组)、MRL/lpr血清组(2组)、MRL/lpr血清+ sirna阴性对照组(3组)、MRL/lpr血清+ siRNA-YAP1组(4组),采用Western blotting和免疫荧光染色检测各组上皮间充质转化(EMT)标志物。采用Spearman分析法检测血清肌酐、尿素氮和尿蛋白水平,并评估其与YAP1 mRNA水平的相关性。结果:与C57BL/6小鼠相比,MRL/lpr小鼠肾组织纤维化有明显改变。此外,MRL/lpr小鼠肾组织中YAP1的表达显著高于C57BL/6小鼠,且YAP1 mRNA水平与FN呈正相关。在狼疮血清刺激细胞中,YAP1沉默可有效缓解血清诱导的EMT。最后,我们观察到小鼠肾组织中YAP1 mRNA水平与肾功能损伤程度呈显著正相关。结论:YAP1在LN小鼠肾组织中的表达高于正常小鼠,提示YAP1可能在LN的发生发展中起重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis.
Objective: The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. Methods: C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. Results: Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. Conclusion: YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.
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