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Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/β-Catenin Signaling Pathway Components

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Abstract

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.

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Acknowledgements

We sincerely thank the writing assistance provided by Dr. Chuang Nie (Department of Epidemiology, College of Public Health, Harbin Medical University) and additional editorial support from American Journal Experts.

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The data during the current study are available from the corresponding author on reasonable request.

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This work was supported financially by the Natural Science Foundation of China (No. 81472929).

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  1. Tingting Lin and Jiaqi Tao contributed equally to this work.

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  1. Department of Biochemistry and Molecular Biology, Harbin Medical University, Baojian Road 157, Nangang District, Harbin City, 150086, Heilongjiang, China

    Tingting Lin, Jiaqi Tao, Ying Chen, Yitong Zhang, Fenglan Li, Yutong Zhang, Xueqing Han, Zihui Zhao, Guiyan Liu & Hui Li

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  1. Tingting Lin
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Lin, T., Tao, J., Chen, Y. et al. Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/β-Catenin Signaling Pathway Components. Biol Trace Elem Res 200, 1127–1139 (2022). https://doi.org/10.1007/s12011-021-02730-1

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