基因敲除
丙二醛
细胞凋亡
脂多糖
化学
流式细胞术
免疫印迹
肿瘤坏死因子α
下调和上调
癌症研究
生存素
分子生物学
败血症
氧化应激
医学
免疫学
生物
生物化学
基因
作者
Wei Lv,Hui Liu,Xin Wang,Rui Hao
出处
期刊:Shock
[Ovid Technologies (Wolters Kluwer)]
日期:2023-11-16
标识
DOI:10.1097/shk.0000000000002271
摘要
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.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 PCR (qRT-PCR). Cell proliferation and apoptosis were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT), thymidine analog 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Secretions of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were detected using ELISA kits. Products of malondialdehyde (MDA) and malondialdehyde (MDA) were measured using Special assay 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 (RIP) assays.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.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.
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