• Shock · May 2024

    Circ_0003907 modulates sepsis-induced myocardial injury via enhancing MYD88/NLRP3/NF-κB axis by sponging miR-944.

    • Wei Lv, Hui Liu, Xin Wang, and Rui Hao.
    • Hypertension/Heart Failure Ward, Central Hospital Affiliated to Shandong First Medical University, Jinan City, China.
    • Shock. 2024 May 1; 61 (5): 705711705-711.

    AbstractBackground : Sepsis-induced cardiomyopathy ( SIC ) is a common complication of sepsis with high morbidity and mortality but lacks specific therapy. The purpose of this study was to investigate the role of circularRNA_0003907 (circ_0003907) in myocardium injury induced by sepsis. Methods: In this experiment, human AC16 cells were treated with lipopolysaccharide (LPS) to induce an in vitro cardiomyocyte injury model. Expression of circ_0003907, microRNA-944 (miR-944), and MYD88 was detected using quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, thymidine analog 5-ethynyl-2'-deoxyuridine, and flow cytometry assays. Secretions of proinflammatory cytokines IL-6 and TNF-α were detected using ELISA kits. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected using special kits. Protein levels of cyclin D1, cleaved caspase-3, MYD88, NLRP3, P65, and IκBα were determined using western blot assay. After being predicted using Circineractome and starBase, the interaction between miR-944 and circ_0003907 or MYD88 was confirmed using dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0003907 expression was increased in serum from SIC patients and in LPS-treated AC16 cells. Circ_0003907 knockdown might abolish LPS-triggered proliferation inhibition, and the promotion of apoptosis, inflammatory response, and oxidative stress in AC16 cells. In mechanism, circ_0003907 acted as a sponge for miR-944 to increase MYD88 expression. Meanwhile, the absence of circ_0003907 induced miR-944 expression and suppressed MYD88/NLRP3/NF-κB levels. Conclusion: Circ_0003907 sponged miR-944 to aggravate LPS-induced AC16 cell dysfunction via activating the MYD88/NLRP3/NF-κB axis during sepsis, which might provide a new direction for the treatment of SIC .Copyright © 2023 by the Shock Society.

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