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MSCs-derived extracellular vesicles alleviate sepsis-associated liver dysfunction by inhibiting macrophage glycolysis-mediated inflammatory response.
Pei, Lei; Li, Ranran; Wang, Xiaofeng; Xu, Dan; Gong, Fangchen; Chen, Weiwei; Zheng, Xiangtao; Liu, Wenbin; Zhao, Shanzhi; Wang, Qiuyun; Mao, Enqiang; Chen, Erzhen; Chen, Ying; Yang, Zhitao.
Afiliación
  • Pei L; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Li R; Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang X; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Xu D; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Gong F; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Chen W; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zheng X; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Liu W; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhao S; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang Q; Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Mao E; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Chen E; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: cez10732@rjh.com.cn.
  • Chen Y; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: cy11530@rjh.com.cn.
  • Yang Z; Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yzt11402@rjh.com.cn.
Int Immunopharmacol ; 128: 111575, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38280334
ABSTRACT
Sepsis-associated liver dysfunction (SALD) aggravates the disease progression and prognosis of patients. Macrophages in the liver play a crucial role in the occurrence and development of SALD. Human umbilical cord mesenchymal stem cells (MSCs), by secreting extracellular vesicles (EVs), show beneficial effects in various inflammatory diseases. However, whether MSC-derived EVs (MSC-EVs) could ameliorate the inflammatory response in liver macrophages and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis induced by lipopolysaccharide (LPS) challenge was used to investigate the immunomodulatory functions of MSC-EVs in SALD. LPS-stimulated primary Kupffer cells (KCs) and Raw264.7 were used to further explore the potential mechanisms of MSC-EVs in regulating the inflammatory response of macrophages. The results showed that MSC-EVs alleviated liver tissue injury and facilitated the polarization of M1 to M2 macrophages. Further in vitro studies confirmed that MSC-EVs treatment significantly downregulated the expression of several enzymes related to glycolysis and reduced the glycolytic flux by inhibiting hypoxia-inducible factor 1α (HIF-1α) expression, thus effectively inhibiting the inflammatory responses of macrophages. These findings reveal that the application of MSC-EVs might be a potential therapeutic strategy for treating SALD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Células Madre Mesenquimatosas / Vesículas Extracelulares / Hepatopatías Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Células Madre Mesenquimatosas / Vesículas Extracelulares / Hepatopatías Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos