Department of Biochemistry and Molecular Biology, Harbin Medical University, Baojian Road 157, Nangang District, Harbin City, 150086, Heilongjiang, China.
Biol Trace Elem Res. 2022 Mar;200(3):1127-1139. doi: 10.1007/s12011-021-02730-1. Epub 2021 Apr 24.
Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored. Thus, this article mainly aimed to investigate the effect of Se deficiency on renal fibrosis and the Wnt/β-catenin signaling pathway. Twenty BALB/c mice were fed a diet containing 0.02-mg/kg Se (Se-deficient diet) or 0.18-mg/kg Se (standard diet) for 20 weeks. A human glomerular mesangial cell (HMC) cell line was transfected with lentiviral TRNAU1AP-shRNA vector to establish a stable Se deficiency model in vitro. As indicated in this study, the glutathione (GSH) content in the Se-deficient group displayed an obvious decline compared with that in the control group, whereas the content of malondialdehyde (MDA) was obviously elevated. The results of Masson staining showed fibrosis around the renal tubules, and the results of immunohistochemistry showed that the area of positive fibronectin expression increased. In the Se-deficient group, the levels of collagen I, collagen III, matrix metalloproteinase 9 (MMP9), and other fibrosis-related proteins changed significantly in vivo and in vitro. Compared with the control group, the TRNAU1AP-shRNA group showed markedly reduced cell proliferation and migration abilities. Our data indicate that Se deficiency can cause kidney damage and renal fibrosis. Furthermore, the Wnt pathway is critical for the development of tissue and organ fibrosis. The data of this study demonstrated that the expression of Wnt5a, β-catenin, and dishevelled 1 (Dvl-1) was significantly upregulated in the Se-deficient group. Therefore, the Wnt/β-catenin pathway may play an important role in renal fibrosis caused by Se deficiency.
肾纤维化是慢性肾脏病(CKD)向终末期肾病(ESRD)进展的最终结果。早期研究证实,硒(Se)与肾脏疾病密切相关。然而,Se 与纤维化之间的相关性很少被探索。因此,本文主要旨在研究 Se 缺乏对肾纤维化和 Wnt/β-catenin 信号通路的影响。将 20 只 BALB/c 小鼠分别用含 0.02mg/kg Se(Se 缺乏饮食)或 0.18mg/kg Se(标准饮食)的饮食喂养 20 周。用慢病毒 TRNAU1AP-shRNA 载体转染人肾小球系膜细胞(HMC)细胞系,建立体外稳定 Se 缺乏模型。本研究结果表明,与对照组相比,Se 缺乏组的谷胱甘肽(GSH)含量明显下降,而丙二醛(MDA)含量明显升高。Masson 染色结果显示肾小管周围纤维化,免疫组化结果显示阳性纤维连接蛋白表达面积增加。在 Se 缺乏组,体内和体外的胶原 I、胶原 III、基质金属蛋白酶 9(MMP9)等纤维化相关蛋白水平均发生明显变化。与对照组相比,TRNAU1AP-shRNA 组细胞增殖和迁移能力明显降低。我们的数据表明,Se 缺乏可导致肾脏损伤和肾纤维化。此外,Wnt 通路对组织和器官纤维化的发展至关重要。本研究的数据表明,在 Se 缺乏组,Wnt5a、β-catenin 和 Dvl-1 的表达明显上调。因此,Wnt/β-catenin 通路可能在 Se 缺乏引起的肾纤维化中发挥重要作用。