The emerging role of neutrophil extracellular traps in liver diseases: a narrative review.

IF 1.4 4区医学 Q3 PATHOLOGY

Medical Molecular Morphology Pub Date : 2026-07-24 DOI:10.1007/s00795-026-00470-6

Lanbao Ye, Yan Chen, Zefeng Liu, Junfeng Ye, Wengang Chai

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引用次数: 0

Abstract

Neutrophil extracellular traps (NETs) are web-like chromatin structures released by neutrophils that play dual roles in host defense and tissue injury. In liver diseases, NETs have emerged as key pathogenic mediators. This narrative review synthesizes current evidence on the involvement of NETs in alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, hepatic ischemia-reperfusion injury (HIRI), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (iCCA). Mechanistically, NETs amplify sterile inflammation, promote hepatocyte death, activate hepatic stellate cells to drive fibrosis. NETs also promote malignant transformation, sustain an aggressive phenotype, attenuate immunotherapy responses, mediate resistance to targeted therapies, and contribute to poor prognosis in primary liver cancers. Preclinical studies targeting NET formation or degrading existing NETs have shown therapeutic benefits across these liver diseases. Despite promising results, clinical translation remains limited, with challenges including a lack of standardized biomarkers, optimal timing of intervention, and the need for liver-specific delivery. This review highlights NETs as a druggable target in liver diseases, and underscores future directions toward biomarker development and targeted therapies.

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中性粒细胞胞外陷阱在肝脏疾病中的新作用：叙述性回顾。

中性粒细胞胞外陷阱（net）是由中性粒细胞释放的网状染色质结构，在宿主防御和组织损伤中起双重作用。在肝脏疾病中，NETs已成为关键的致病介质。这篇叙述性综述综合了目前关于NETs参与酒精相关肝病（ALD）、代谢功能障碍相关脂肪变性肝病（MASLD）、病毒性肝炎、肝缺血再灌注损伤（HIRI）、肝细胞癌（HCC）和肝内胆管癌（iCCA）的证据。从机制上讲，NETs放大无菌性炎症，促进肝细胞死亡，激活肝星状细胞驱动纤维化。NETs还促进恶性转化，维持侵袭性表型，减弱免疫治疗反应，介导对靶向治疗的抵抗，并导致原发性肝癌预后不良。针对NET形成或降解现有NET的临床前研究已显示出对这些肝脏疾病的治疗益处。尽管取得了令人鼓舞的结果，但临床转化仍然有限，面临的挑战包括缺乏标准化的生物标志物、最佳干预时间和需要肝脏特异性递送。这篇综述强调了NETs作为肝脏疾病的可药物靶点，并强调了生物标志物开发和靶向治疗的未来方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.