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慢性阻塞性肺疾病中的cGAS-STING信号通路:靶向其作用及治疗潜力

The cGAS-STING pathway in COPD: targeting its role and therapeutic potential.

作者信息

Liao Kexin, Wang Fengshuo, Xia Chenhao, Xu Ze, Zhong Sen, Bi Wenqi, Ruan Jingjing

机构信息

First Clinical Medical College, Anhui Medical University, Hefei, 230022, People's Republic of China.

College of Pharmacy, Anhui Medical University, Hefei, 230022, People's Republic of China.

出版信息

Respir Res. 2024 Aug 7;25(1):302. doi: 10.1186/s12931-024-02915-x.

DOI:10.1186/s12931-024-02915-x
PMID:39113033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11308159/
Abstract

Chronic obstructive pulmonary disease(COPD) is a gradually worsening and fatal heterogeneous lung disease characterized by airflow limitation and increasingly decline in lung function. Currently, it is one of the leading causes of death worldwide. The consistent feature of COPD is airway inflammation. Several inflammatory factors are known to be involved in COPD pathogenesis; however, anti-inflammatory therapy is not the first-line treatment for COPD. Although bronchodilators, corticosteroids and roflumilast could improve airflow and control symptoms, they could not reverse the disease. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway plays an important novel role in the immune system and has been confirmed to be a key mediator of inflammation during infection, cellular stress, and tissue damage. Recent studies have emphasized that abnormal activation of cGAS-STING contributes to COPD, providing a direction for new treatments that we urgently need to develop. Here, we focused on the cGAS-STING pathway, providing insight into its molecular mechanism and summarizing the current knowledge on the role of the cGAS-STING pathway in COPD. Moreover, we explored antagonists of cGAS and STING to identify potential therapeutic strategies for COPD that target the cGAS-STING pathway.

摘要

慢性阻塞性肺疾病(COPD)是一种逐渐恶化且致命的异质性肺部疾病,其特征为气流受限以及肺功能日益下降。目前,它是全球主要死因之一。COPD的一致特征是气道炎症。已知多种炎症因子参与COPD的发病机制;然而,抗炎治疗并非COPD的一线治疗方法。尽管支气管扩张剂、皮质类固醇和罗氟司特可改善气流并控制症状,但它们无法逆转疾病。环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激物(cGAS-STING)信号通路在免疫系统中发挥着重要的新作用,并且已被证实是感染、细胞应激和组织损伤期间炎症的关键介质。最近的研究强调,cGAS-STING的异常激活促成了COPD,为我们迫切需要开发的新治疗方法提供了方向。在此,我们聚焦于cGAS-STING通路,深入了解其分子机制,并总结当前关于cGAS-STING通路在COPD中作用的知识。此外,我们探索了cGAS和STING的拮抗剂,以确定针对cGAS-STING通路的COPD潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/11308159/349108a8566e/12931_2024_2915_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/11308159/349108a8566e/12931_2024_2915_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/11308159/349108a8566e/12931_2024_2915_Fig1_HTML.jpg

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本文引用的文献

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cGAS-STING drives ageing-related inflammation and neurodegeneration.cGAS-STING 驱动与衰老相关的炎症和神经退行性变。
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The global economic burden of chronic obstructive pulmonary disease for 204 countries and territories in 2020-50: a health-augmented macroeconomic modelling study.2020-50 年全球 204 个国家和地区慢性阻塞性肺疾病的全球经济负担:一项健康增强型宏观经济建模研究。
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Hallmarks of aging: An expanding universe.衰老的特征:一个不断扩大的领域。
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Inflammatory Biomarkers Interleukin 1 Beta (IL-1β) and Tumour Necrosis Factor Alpha (TNF-α) Are Differentially Elevated in Tobacco Smoke Associated COPD and Biomass Smoke Associated COPD.炎症生物标志物白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)在烟草烟雾相关慢性阻塞性肺疾病(COPD)和生物质烟雾相关COPD中升高情况存在差异。
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