Scholarlink

<p>Hepatic ischemia-reperfusion injury (IRI) is a serious complication during liver transplantation, which triggers a strongrepresents a significant complication in the context of liver transplantation, characterized by the induction of a robust non-specific inflammatory response throughmediated by damage-associated molecular patterns (DAMPs) and leads to, ultimately resulting in dysfunction of the transplanted liverorgan. The pathogenic pro-inflammatory (M1) polarization of hepatic macrophages is a driver of this hepatocyte injury, but the exact upstream trigger factor for this remains unclear. We investigated thecritical contributor to this hepatocellular damage; however, the precise upstream trigger remains unidentified. This study explores the potential role of neutrophil extracellular traps (NETs) as an upstream regulator of M1-type macrophage polarization. Utilizing the in vivo H-IRI mouse model alongside an in vitro macrophage co-culture system, we elucidated that the interaction between neutrophil extracellular traps (NETs) and macrophages is facilitated by the cGAS-STING signaling pathway. Our findings indicate that the double-stranded DNA generated by NETs is internalized by macrophages, subsequently activating the cytoplasmic sensor cGAS and the adaptor protein 3wSTING. This activation serves as a driver for the M1 macrophage phenotype. Our study unveils a novel and critical pathway, “NETs → cGAS-STING → M1 polarization,” which plays a significant role in hepatic ischemia-reperfusion injury (HIRI). This pathway presents a promising therapeutic target for mitigating graft damage following liver transplantation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neutrophil extracellular traps exacerbate liver ischemia-reperfusion injury by promoting macrophage M1 polarization via the cGAS-STING pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月24日

查看全文
  • Dingheng Hu,
  • Yunhai Luo,
  • Liangxu Wang,
  • Zhengli Tan,
  • Qi Li,
  • Denghui Wang,
  • Zhongjun Wu

摘要

Hepatic ischemia-reperfusion injury (IRI) is a serious complication during liver transplantation, which triggers a strongrepresents a significant complication in the context of liver transplantation, characterized by the induction of a robust non-specific inflammatory response throughmediated by damage-associated molecular patterns (DAMPs) and leads to, ultimately resulting in dysfunction of the transplanted liverorgan. The pathogenic pro-inflammatory (M1) polarization of hepatic macrophages is a driver of this hepatocyte injury, but the exact upstream trigger factor for this remains unclear. We investigated thecritical contributor to this hepatocellular damage; however, the precise upstream trigger remains unidentified. This study explores the potential role of neutrophil extracellular traps (NETs) as an upstream regulator of M1-type macrophage polarization. Utilizing the in vivo H-IRI mouse model alongside an in vitro macrophage co-culture system, we elucidated that the interaction between neutrophil extracellular traps (NETs) and macrophages is facilitated by the cGAS-STING signaling pathway. Our findings indicate that the double-stranded DNA generated by NETs is internalized by macrophages, subsequently activating the cytoplasmic sensor cGAS and the adaptor protein 3wSTING. This activation serves as a driver for the M1 macrophage phenotype. Our study unveils a novel and critical pathway, “NETs → cGAS-STING → M1 polarization,” which plays a significant role in hepatic ischemia-reperfusion injury (HIRI). This pathway presents a promising therapeutic target for mitigating graft damage following liver transplantation.