• Shock · Jan 2024

    CircUSP42 ameliorates LPS-induced human renal epithelial cells in vitro by regulating the miR-182-5p/DUSP1 axis.

    • Shu Luo, Mengqin Li, Xuefeng Ding, Feng Luo, and Zhangping Liao.
    • Department of Emergency, Affiliated Hospital of North Sichuan Medical College, Nanchong City, China.
    • Shock. 2024 Jan 1; 61 (1): 414841-48.

    AbstractBackground: Sepsis is a life-threatening systemic inflammatory disease that can cause many diseases, including acute kidney injury (AKI). Increasing evidence showed that a variety of circular RNAs were considered to be involved in the development of the disease. In this study, we aimed to elucidate the role and potential mechanism of circUSP42 in sepsis-induced AKI. Methods: HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. The expression levels of circUSP42, microRNA-182-5p (miR-182-5p), and DUSP1 in LPS-treated HK2 cells were measured by quantitative real-time polymerase chain reaction or Western blot. Functional experiments were performed by using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, oxidative stress assay, and enzyme-linked immunosorbent assay. The potential target binding site between miR-182-5p and CircUSP42 or DUSP1 was verified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: CircUSP42 and DUSP1 were downregulated in serum samples from patients with AKI and LPS-treated HK2 cells, while miR-182-5p was upregulated. Functionally, overexpression of CircUSP42 promoted cell proliferation and inhibited apoptosis, inflammation, and oxidative stress in LPS-triggered HK2 cells. Further mechanism analysis showed that miR-182-5p had potential binding sites with circUSP42 and DUSP1, and circUSP42 regulated LPS-induced cell damage by targeting miR-182-5p. At the same time, miR-182-5p knockdown inhibited LPS-treated HK2 cell damage by regulating DUSP1. In addition, circUSP42 induced DUSP1 expression via sponging miR-182-5p to ameliorate LPS-induced HK2 cell damage. Conclusion : Our results showed that circUSP42 overexpression might attenuate LPS-induced HK2 cell injury by regulating miR-182-5p/DUSP1 axis. This might provide therapeutic strategy for the treatment of sepsis.Copyright © 2023 by the Shock Society.

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