心肌梗塞(MI)是由于动脉内壁中斑块的形成而引起的心脏病发作事件。本研究旨在探讨泛素特异性肽酶47(USP47)在心脏功能和炎症免疫中的作用。建立MI小鼠模型,然后是心脏功能的评估,梗死面积,病理变化,和USP47和NLRP3水平。利用缺氧在HL-1细胞中建立MI细胞模型。心功能相关蛋白的水平,USP7,干扰素调节因子1(IRF1),血小板因子4(CXCL4),热解因子,并测定中性粒细胞胞外诱捕网(NETs)。分析了IRF1与USP47和CXCL4启动子的结合以及IRF1的泛素化。USP47在MI小鼠的心肌组织中上调。USP47抑制减轻心脏功能,梗死面积减少,促炎细胞因子,NET,NLRP3和焦亡。通过沉默USP47增加IRF1的泛素化和表达水平,并且IRF1与CXCL4启动子结合以促进CXCL4。体外IRF1或CXCL4的过表达和体内注射Nigericin逆转了沉默USP47减轻细胞凋亡和心脏功能的作用。总的来说,USP47稳定IRF1并促进CXCL4,进一步促进焦亡,损害心脏功能,并通过NLRP3途径加重免疫炎症。
Myocardial infarction (MI) is an event of heart attack due to the formation of plaques in the interior walls of the arteries. This study is conducted to explore the role of ubiquitin-specific peptidase 47 (USP47) in cardiac function and inflammatory immunity. MI mouse models were established, followed by an appraisal of cardiac functions, infarct size, pathological changes, and USP47 and NLRP3 levels. MI cell models were established in HL-1 cells using anoxia. Levels of cardiac function-associated proteins, USP7, interferon regulatory factor 1 (
IRF1), platelet factor-4 (CXCL4), pyroptotic factors, and neutrophil extracellular traps (NETs) were determined. The bindings of
IRF1 to USP47 and the CXCL4 promoter and the ubiquitination of
IRF1 were analyzed. USP47 was upregulated in myocardial tissues of MI mice. USP47 inhibition alleviated cardiac functions, and decreased infarct size, pro-inflammatory cytokines, NETs, NLRP3, and pyroptosis. The ubiquitination and expression levels of
IRF1 were increased by silencing USP47, and
IRF1 bound to the CXCL4 promoter to promote CXCL4. Overexpression of
IRF1 or CXCL4 in vitro and injection of Nigericin in vivo reversed the effect of silencing USP47 on alleviating pyroptosis and cardiac functions. Collectively, USP47 stabilized
IRF1 and promoted CXCL4, further promoting pyroptosis, impairing cardiac functions, and aggravating immune inflammation through NLRP3 pathways.