1. Academic Validation
  2. Role of deubiquitinase USP47 in cardiac function alleviation and anti-inflammatory immunity after myocardial infarction by regulating NLRP3 inflammasome-mediated pyroptotic signal pathways

Role of deubiquitinase USP47 in cardiac function alleviation and anti-inflammatory immunity after myocardial infarction by regulating NLRP3 inflammasome-mediated pyroptotic signal pathways

  • Int Immunopharmacol. 2024 Jul 30:136:112346. doi: 10.1016/j.intimp.2024.112346.
Zheng Wu 1 Wenzheng Li 2 Shaoping Wang 2 Ze Zheng 2
Affiliations

Affiliations

  • 1 Center for Coronary Artery Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address: zhengwu2161@163.com.
  • 2 Center for Coronary Artery Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Abstract

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.

Keywords

CXCL4; IRF1; Myocardial infarction; NLRP3; Pyroptosis; USP47.

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