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中性粒细胞凋亡调节中的特异性促消退介质:挖掘肾脏疾病的新型治疗潜力

Specialized pro-resolving mediators in neutrophil apoptosis regulation: unlocking novel therapeutic potential in kidney diseases.

作者信息

Kang Yi, Jin Qian, Zhou Mengqi, Zheng Huijuan, Li Danwen, Wang Xuezhe, Zhou Jingwei, Wang Yaoxian, Lv Jie

机构信息

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Immunol. 2025 May 15;16:1589923. doi: 10.3389/fimmu.2025.1589923. eCollection 2025.

Abstract

Kidney diseases represent a diverse group of disorders with pathogenic mechanisms involving multiple pathological processes, including inflammation, immunity, and cell death. Neutrophils, as primary effector cells in inflammatory immune responses, participate in defending against renal infection and injury by releasing reactive oxygen species, proteases, and cytokines. However, persistent neutrophil activation is considered a crucial driver of kidney disease progression. Neutrophil apoptosis represents a critical turning point between inflammatory progression and resolution. Specialized pro-resolving mediators (SPMs) are endogenous anti-inflammatory mediators that play a critical role in resolving inflammation. They not only induce neutrophil programmed cell death and promote macrophage-mediated efferocytosis of apoptotic cells but also inhibit neutrophil infiltration and degranulation, ultimately facilitating the restoration of inflammatory microenvironment and tissue homeostasis. This review concentrates on elucidating the mechanisms by which SPMs regulate neutrophil apoptosis and systematically demonstrates their potential as novel therapeutic targets in kidney diseases.

摘要

肾脏疾病是一组多样化的病症,其致病机制涉及多种病理过程,包括炎症、免疫和细胞死亡。中性粒细胞作为炎症免疫反应中的主要效应细胞,通过释放活性氧、蛋白酶和细胞因子参与抵御肾脏感染和损伤。然而,持续的中性粒细胞活化被认为是肾脏疾病进展的关键驱动因素。中性粒细胞凋亡是炎症进展与消退之间的关键转折点。专门的促消退介质(SPM)是内源性抗炎介质,在解决炎症方面发挥着关键作用。它们不仅诱导中性粒细胞程序性细胞死亡并促进巨噬细胞介导的凋亡细胞吞噬作用,还抑制中性粒细胞浸润和脱颗粒,最终促进炎症微环境和组织稳态的恢复。本综述专注于阐明SPM调节中性粒细胞凋亡的机制,并系统地展示它们作为肾脏疾病新型治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e07c/12119277/a0eb12db9adf/fimmu-16-1589923-g001.jpg

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