The cGAS-STING axis in kidney disease: mechanisms and therapeutic potential

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2025-09-16 DOI:10.1016/j.ejphar.2025.178155

Jing Li , Xiaoqin Liu , Haoyue Feng

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引用次数: 0

Abstract

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis is a pivotal innate immune signaling pathway that detects cytoplasmic DNA and initiates immune responses. Recent studies have highlighted its critical role in the pathogenesis of various kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease, lupus nephritis, and kidney cancer. Dysregulated cGAS-STING activation contributes to renal inflammation, fibrosis, and disease progression, making it a promising therapeutic target. This review explores the involvement of the cGAS-STING pathway in multiple renal disorders, emphasizing its dual roles in disease progression and immune regulation. Additionally, we discuss potential therapeutic strategies, including small-molecule inhibitors, agonists, and Traditional Chinese Medicine (TCM) formulations, that may modulate this pathway to attenuate kidney injury. Despite its therapeutic promise, the cGAS-STING axis exhibits complex and context-dependent regulation, with varying effects across different renal diseases. Further research is needed to elucidate its precise molecular mechanisms and optimize targeted interventions for clinical translation.

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肾脏疾病中的cGAS-STING轴：机制和治疗潜力。

干扰素基因（STING）轴环GMP-AMP合成酶（cGAS）刺激因子是检测细胞质DNA并启动免疫应答的关键先天免疫信号通路。近年来的研究强调了它在各种肾脏疾病的发病机制中的重要作用，包括急性肾损伤、慢性肾病、糖尿病肾病、狼疮肾炎和肾癌。失调的cGAS-STING激活有助于肾脏炎症、纤维化和疾病进展，使其成为一个有希望的治疗靶点。本文探讨了cGAS-STING通路在多种肾脏疾病中的作用，强调了其在疾病进展和免疫调节中的双重作用。此外，我们还讨论了潜在的治疗策略，包括小分子抑制剂、激动剂和中药制剂，它们可能调节这一途径以减轻肾损伤。尽管具有治疗前景，但cGAS-STING轴表现出复杂的环境依赖性调控，在不同的肾脏疾病中具有不同的作用。需要进一步的研究来阐明其精确的分子机制并优化临床转化的靶向干预措施。

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

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.