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Role of uromodulin and complement activation in the progression of kidney disease

  • Authors:
    • Fei Shen
    • Maojing Liu
    • Fei Pei
    • Li Yu
    • Xiangdong Yang
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Qi Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
    Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 829
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    Published online on: October 13, 2021
       https://doi.org/10.3892/ol.2021.13090
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Abstract

Uromodulin (UMOD) is a glycoprotein that is selectively expressed on the epithelial cells of the thick ascending limb of Henle's loop and the early distal renal tubule. The present study aimed to investigate whether UMOD was associated with complement activation in patients with renal diseases. In addition, its biological function was examined in vitro. The expression levels of UMOD and complement components, including C1q, C3, C4 and C3a, and membrane attack complex (MAC) in the plasma of patients with IgA nephropathy (IgAN; n=58) and lupus nephritis (LN; n=36) were detected using ELISA, which was used to determine the association between UMOD expression and complement components. In addition, a simulated hypoxia‑reoxygenation (H/R) model was used to stimulate UMOD expression in mouse inner medullary collecting duct cells. Additionally, the association between UMOD expression and complement components C1q and C3d at the cellular level was identified using western blotting and immunofluorescence, respectively. It was revealed that the plasma UMOD concentration was significantly decreased in patients with IgAN and LN compared with in healthy controls, and the levels of C3a and MAC were significantly increased in the plasma of patients with IgAN and LN. Furthermore, the plasma levels of C1q, C3 and C4 in patients with LN, but not in patients with IgAN, were significantly decreased compared with in healthy controls. The plasma levels of UMOD were negatively correlated with the plasma C3a and MAC concentrations. However, the plasma levels of UMOD were significantly and positively correlated with the plasma C1q concentration, but not with that of C3 and C4. It was identified that UMOD expression started to increase after 1 h of simulated H/R, and continued to increase at 6 and 12 h. In addition, cells with lower UMOD expression had higher C3d expression in vitro. Collectively, the present results suggested that UMOD was associated with severe complement activation and may be involved in complement‑mediated immune protection by inhibiting complement activation in renal disease.
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Copy and paste a formatted citation
Spandidos Publications style
Shen F, Liu M, Pei F, Yu L and Yang X: Role of uromodulin and complement activation in the progression of kidney disease. Oncol Lett 22: 829, 2021.
APA
Shen, F., Liu, M., Pei, F., Yu, L., & Yang, X. (2021). Role of uromodulin and complement activation in the progression of kidney disease. Oncology Letters, 22, 829. https://doi.org/10.3892/ol.2021.13090
MLA
Shen, F., Liu, M., Pei, F., Yu, L., Yang, X."Role of uromodulin and complement activation in the progression of kidney disease". Oncology Letters 22.6 (2021): 829.
Chicago
Shen, F., Liu, M., Pei, F., Yu, L., Yang, X."Role of uromodulin and complement activation in the progression of kidney disease". Oncology Letters 22, no. 6 (2021): 829. https://doi.org/10.3892/ol.2021.13090
Copy and paste a formatted citation
x
Spandidos Publications style
Shen F, Liu M, Pei F, Yu L and Yang X: Role of uromodulin and complement activation in the progression of kidney disease. Oncol Lett 22: 829, 2021.
APA
Shen, F., Liu, M., Pei, F., Yu, L., & Yang, X. (2021). Role of uromodulin and complement activation in the progression of kidney disease. Oncology Letters, 22, 829. https://doi.org/10.3892/ol.2021.13090
MLA
Shen, F., Liu, M., Pei, F., Yu, L., Yang, X."Role of uromodulin and complement activation in the progression of kidney disease". Oncology Letters 22.6 (2021): 829.
Chicago
Shen, F., Liu, M., Pei, F., Yu, L., Yang, X."Role of uromodulin and complement activation in the progression of kidney disease". Oncology Letters 22, no. 6 (2021): 829. https://doi.org/10.3892/ol.2021.13090
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