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Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway

  • Authors:
    • Dongdong Li
    • Luobing Wang
    • Jiaoying Ou
    • Chuanxu Wang
    • Jiabao Zhou
    • Lili Lu
    • Yanshneg Wu
    • Jiandong Gao
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, P.R. China, Department of Internal Medicine, Shanghai TCM‑Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 729
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    Published online on: August 13, 2021
       https://doi.org/10.3892/mmr.2021.12368
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Abstract

Increasing uric acid (UA) could induce renal tubular epithelial cell (NRK‑52E) injury. However, the specific mechanism by which UA induces renal tubular epithelial cell injury remains unknown. It was hypothesized that UA induces renal tubular epithelial cell injury through reactive oxygen species (ROS) and the Never in mitosis gene A (NIMA)‑related kinase 7 (NEK7)/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. TUNEL assay and flow cytometry were applied to measure apoptosis, and the results of the present study showed that UA treatment induced apoptosis of NRK‑52E cells in a concentration‑dependent manner. Western blotting was performed to determine the expression levels of cleaved caspase‑3, Bax and Bcl‑xl, it was found that levels were significantly increased after UA treatment in NRK‑52E cells. ROS and apoptosis were predominantly induced in NRK‑52E cells and there was an association between ROS and apoptosis. Enhanced expression of NEK7, NLRP3, apoptosis‑associated speck‑like and caspase‑1 were observed in NRK‑52E cells treated with UA. The ROS inhibitor, N‑acetyl‑l‑cysteine, exerted a protective effect on the UA‑induced apoptosis of tubular epithelial cells by reducing excess ROS production, which significantly inhibited NEK7 and NLRP3 inflammasome activation. These results indicated that UA activates ROS and induces apoptosis of NRK‑52E cells. The mechanism might be related to the regulation of the NEK7/NLRP3 signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Li D, Wang L, Ou J, Wang C, Zhou J, Lu L, Wu Y and Gao J: Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway. Mol Med Rep 24: 729, 2021.
APA
Li, D., Wang, L., Ou, J., Wang, C., Zhou, J., Lu, L. ... Gao, J. (2021). Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway. Molecular Medicine Reports, 24, 729. https://doi.org/10.3892/mmr.2021.12368
MLA
Li, D., Wang, L., Ou, J., Wang, C., Zhou, J., Lu, L., Wu, Y., Gao, J."Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway". Molecular Medicine Reports 24.4 (2021): 729.
Chicago
Li, D., Wang, L., Ou, J., Wang, C., Zhou, J., Lu, L., Wu, Y., Gao, J."Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway". Molecular Medicine Reports 24, no. 4 (2021): 729. https://doi.org/10.3892/mmr.2021.12368
Copy and paste a formatted citation
x
Spandidos Publications style
Li D, Wang L, Ou J, Wang C, Zhou J, Lu L, Wu Y and Gao J: Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway. Mol Med Rep 24: 729, 2021.
APA
Li, D., Wang, L., Ou, J., Wang, C., Zhou, J., Lu, L. ... Gao, J. (2021). Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway. Molecular Medicine Reports, 24, 729. https://doi.org/10.3892/mmr.2021.12368
MLA
Li, D., Wang, L., Ou, J., Wang, C., Zhou, J., Lu, L., Wu, Y., Gao, J."Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway". Molecular Medicine Reports 24.4 (2021): 729.
Chicago
Li, D., Wang, L., Ou, J., Wang, C., Zhou, J., Lu, L., Wu, Y., Gao, J."Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway". Molecular Medicine Reports 24, no. 4 (2021): 729. https://doi.org/10.3892/mmr.2021.12368
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