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.
Pathobiology

中文翻译：

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YAP1过表达与狼疮性肾炎肾功能障碍有关

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，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。取出小鼠肾组织并切片用于苏木精和伊红染色、Masson 毛状体染色、天狼星染色和免疫组织化学。检测小鼠肾组织中YAP1的mRNA和蛋白水平，分析YAP1与纤连蛋白（FN）mRNA水平的相关性。小鼠肾上皮细胞用于体外实验。转染刺激后细胞分为4组，即C57BL/6血清组（第1组）、MRL/lpr血清组（第2组）、MRL/lpr血清+siRNA阴性对照组（第3组） ）和 MRL/lpr 血清 + siRNA-YAP1 组（第 4 组）。采用Western blotting和免疫荧光染色检测各组上皮-间质转化(EMT)标志物。血清肌酐，结果：与C57BL/6小鼠相比，MRL/lpr小鼠肾组织纤维化有明显变化。此外，MRL/lpr小鼠肾组织中YAP1的表达明显高于C57BL/6小鼠，且YAP1 mRNA水平与FN呈正相关。狼疮血清刺激细胞中的 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着正相关。结论： LN小鼠肾组织中YAP1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。
病理学