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MicroRNA-223 downregulation promotes HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome

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A Correction to this article was published on 22 August 2023

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Abstract

Hepatitis B virus (HBV) and its related protein, HBV X (HBx), play an important role in podocyte injury in HBV-associated glomerulonephritis (HBV-GN). The microRNA MiR-223 is expressed in several diseases, including HBV-associated disease, while the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a major role in pyroptosis. In this study, we investigated the function and mechanism of action of miR-223 in HBx-induced podocyte pyroptosis. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assay showed that miR-223 was downregulated in HBx-transfected podocytes. Transfection with an miR-223 mimic abolished the expression of the NLRP3 inflammasome and the cytokines that are released as a result of NLRP3 overexpression. Moreover, transfection with HBx and NLRP3 overexpression plasmids increased the expression of pyroptosis-related proteins, especially in the presence of miR-223 inhibitors. Thus, miR-223 downregulation plays an important role in HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome, suggesting that miR-223 is a potential therapeutic target for alleviating HBV-GN inflammation.

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Funding

This work was supported by the National Natural Science Foundation of China (grant number NSFC 81870494), the Chinese Society of Nephrology (grant number 20010080800), and the Qingdao Outstanding Health Professional Development Fund (grant number 2020-2022).

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Author notes

  1. Yani Yu and Hui Dong contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China

    Yani Yu, Jingyi Sun, Baoshuang Li, Yueqi Chen, Moxuan Feng, Xiaoqian Yang & Wei Jiang

  2. Health Management Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China

    Hui Dong

  3. Department of Stomatology, Qingdao Municipal Hospital Group, Qingdao, 266003, Shandong, China

    Yue Zhang

  4. Department of Nephrology, The People’s Hospital of Changle County, Weifang, 262400, Shandong, China

    Shengbo Gao

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  1. Yani Yu
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Contributions

Yani YU, Hui DONG, and Wei JIANG designed the experimental idea and wrote the main manuscript text. Yue ZHANG, Jingyi SUN, and Baoshuang LI performed the experiments and collected the relevant data. Yueqi CHEN, Moxuan FENG, and Xiaoqian YANG finished the formal analysis and investigation. Shengbo GAO prepared Figures 1-5. All authors reviewed the manuscript.

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Correspondence to Wei Jiang.

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Approval was granted by the Affiliated Hospital of Qingdao University. All methods were performed in accordance with the relevant guidelines and regulations.

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Yu, Y., Dong, H., Zhang, Y. et al. MicroRNA-223 downregulation promotes HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome. Arch Virol 167, 1841–1854 (2022). https://doi.org/10.1007/s00705-022-05499-3

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