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子宫腺肌病患者中 cGAS-STING 信号通路的激活。

Activation of the cGAS-STING signaling pathway in adenomyosis patients.

机构信息

Department of Obstetrics and Gynecology, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

Immun Inflamm Dis. 2021 Sep;9(3):932-942. doi: 10.1002/iid3.452. Epub 2021 May 19.

DOI:10.1002/iid3.452
PMID:34010983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8342233/
Abstract

OBJECTIVE

Adenomyosis is characterized by the presence of endometrium or endometrium-like glands and stroma within the myometrium. In this study, we aimed to investigate whether the cGAS-STING pathway was activated and correlated with clinical outcomes in adenomyosis patients.

MATERIALS AND METHODS

Twenty patients diagnosed with adenomyosis and 10 patients diagnosed with cervical intraepithelial neoplasia grade 3 (CIN-3) but no adenomyosis were enrolled in this study. Specimens were collected during surgery from August 2017 to December 2017 at Third Xiangya Hospital. The messenger RNA (mRNA) and protein levels of key cGAS-STING pathway factors in uterine tissue were detected by real-time reverse-transcription polymerase chain reaction and immunohistochemistry, respectively. The correlations of gene expression and clinical outcomes, including dysmenorrhea and uterine volume, were analyzed.

RESULTS

The cGAS, STING, TANK-binding kinase 1 (TBK-1), interferon-α (IFN-α), IFN-β, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in the ectopic endometrial tissue from adenomyosis patients were significantly higher compared with that from the controls in endometrium (p < .05). cGAS and STING gene expression were correlated with TBK-1, IFN-β, and TNF-α expression (p < .05). Importantly, TBK-1 and TNF-α expression were correlated with the clinical outcome of dysmenorrhea (p < .05).

CONCLUSION

Our study reveals that the cGAS-STING pathway is activated in adenomyosis patients and its activation is subsequently correlated with clinical outcomes, which suggests that the cGAS-STING pathway may contribute to adenomyosis pathogenesis.

摘要

目的

子宫腺肌病的特征是子宫内膜或类似子宫内膜的腺体和基质存在于子宫肌层中。本研究旨在探讨 cGAS-STING 通路是否在子宫腺肌病患者中被激活,并与临床结局相关。

材料和方法

本研究纳入了 20 例子宫腺肌病患者和 10 例宫颈上皮内瘤变 3 级(CIN-3)但无子宫腺肌病的患者。标本采集于 2017 年 8 月至 2017 年 12 月于湘雅三医院。通过实时逆转录聚合酶链反应和免疫组织化学分别检测子宫组织中关键 cGAS-STING 通路因子的信使 RNA(mRNA)和蛋白水平。分析基因表达与临床结局(痛经和子宫体积)的相关性。

结果

与对照组的子宫内膜相比,子宫腺肌病患者的异位子宫内膜组织中的 cGAS、STING、TANK 结合激酶 1(TBK-1)、干扰素-α(IFN-α)、干扰素-β(IFN-β)和肿瘤坏死因子-α(TNF-α)mRNA 和蛋白水平显著升高(p < .05)。cGAS 和 STING 基因表达与 TBK-1、IFN-β 和 TNF-α表达相关(p < .05)。重要的是,TBK-1 和 TNF-α的表达与痛经的临床结局相关(p < .05)。

结论

本研究揭示 cGAS-STING 通路在子宫腺肌病患者中被激活,其激活与临床结局相关,提示 cGAS-STING 通路可能参与子宫腺肌病的发病机制。

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The cGAS-cGAMP-STING Pathway: A Molecular Link Between Immunity and Metabolism.cGAS-cGAMP-STING 通路:免疫与代谢之间的分子联系。
Diabetes. 2019 Jun;68(6):1099-1108. doi: 10.2337/dbi18-0052.
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The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer.cGAS-cGAMP-STING 通路将 DNA 损伤与炎症、衰老和癌症联系起来。
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Pathogenesis of adenomyosis: an update on molecular mechanisms.子宫腺肌病的发病机制:分子机制的最新研究进展。
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Regulating STING in health and disease.调控健康与疾病中的STING蛋白。
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DNA sensor cGAS-mediated immune recognition.DNA 传感器 cGAS 介导的免疫识别。
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Involvement of NADPH oxidase and NF-κB activation in CXCL1 induction by vascular endothelial growth factor in human endometrial epithelial cells of patients with adenomyosis.NADPH氧化酶和NF-κB激活在子宫腺肌病患者人子宫内膜上皮细胞中血管内皮生长因子诱导CXCL1过程中的作用
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