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MG53 protects against Coxsackievirus B3-induced acute viral myocarditis in mice by inhibiting NLRP3 inflammasome-mediated pyroptosis via the NF-κB signaling pathway.
Xue, Yimin; Song, Tianjiao; Ke, Jun; Lin, Shirong; Zhang, Jiuyun; Chen, Yimei; Wang, Junyi; Fan, Qiaolian; Chen, Feng.
Afiliación
  • Xue Y; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Fourth Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Song T; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Ke J; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Lin S; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Zhang J; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Chen Y; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Wang J; Department of Intensive Care Unit, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, Fujian, China.
  • Fan Q; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Fourth Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China.
  • Chen F; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, Fujian, China. Electronic address: fjslchenfeng@126.com.
Biochem Pharmacol ; 223: 116173, 2024 05.
Article en En | MEDLINE | ID: mdl-38552849
ABSTRACT
Pyroptosis, a novel programmed cell death mediated by NOD-like receptor protein 3 (NLRP3) inflammasome, is a critical pathogenic process in acute viral myocarditis (AVMC). Mitsugumin 53 (MG53) is predominantly expressed in myocardial tissues and has been reported to exert cardioprotective effects through multiple pathways. Herein, we aimed to investigate the biological function of MG53 in AVMC and its underlying regulatory mechanism in pyroptosis. BALB/c mice and HL-1 cells were infected with Coxsackievirus B3 (CVB3) to establish animal and cellular models of AVMC. As inflammation progressed in the myocardium, we found a progressive decrease in myocardial MG53 expression, accompanied by a significant enhancement of cardiomyocyte pyroptosis. MG53 overexpression significantly alleviated myocardial inflammation, apoptosis, fibrosis, and mitochondrial damage, thereby improving cardiac dysfunction in AVMC mice. Moreover, MG53 overexpression inhibited NLRP3 inflammasome-mediated pyroptosis, reduced pro-inflammatory cytokines (IL-1ß/18) release, and suppressed NF-κB signaling pathway activation both in vivo and in vitro. Conversely, MG53 knockdown reduced cell viability, facilitated cell pyroptosis, and increased pro-inflammatory cytokines release in CVB3-infected HL-1 cells by promoting NF-κB activation. These effects were partially reversed by applying the NF-κB inhibitor BAY 11-7082. In conclusion, our results suggest that MG53 acts as a negative regulator of NLRP3 inflammasome-mediated pyroptosis in CVB3-induced AVMC, partially by inhibiting the NF-κB signaling pathway. MG53 is a promising candidate for clinical applications in AVMC treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Miocarditis Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Miocarditis Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido