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环鸟苷酸-腺苷酸合酶在人根尖周炎中的表达:一项实验室研究。

The expression of cyclic GMP-AMP synthase in human apical periodontitis: A laboratory investigation.

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Centre for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Int Endod J. 2023 Jun;56(6):710-721. doi: 10.1111/iej.13904. Epub 2023 Feb 27.

Abstract

AIM

As a key DNA sensor, cyclic GMP-AMP synthase (cGAS) has emerged as a major mediator of innate immunity and inflammation. Human apical periodontitis has yet to be studied for the presence of cGAS. This investigation was conducted to determine if cGAS is involved in the pathological process of human apical periodontitis.

METHODOLOGY

Sixty four human periapical lesions, comprising 20 periapical granulomas and 44 radicular cysts, were employed in this investigation. Healthy gingiva (n = 6), dental pulp (n = 3), and apical papilla (n = 3) were used as control samples. The expression of cGAS in the periapical tissues was discovered using immunohistochemical staining. mRNA-Sequencing and qRT-PCR were utilized to determine the differentially expressed genes (DEGs) associated with DNA-sensing signalling in periapical lesions compared to the healthy control. Immunofluorescence labelling was used to identify the co-expression of cGAS, interleukin-1β, and interleukin-18.

RESULTS

A significantly greater expression level of cGAS was discovered in the periapical lesions, with no significant difference between radicular cysts and periapical granulomas. mRNA-Sequencing analysis and qRT-PCR identified differentially expressed mRNA, such as cGAS and its downstream DEGs, between periapical lesions and healthy control tissues. Immunofluorescence labelling further revealed that cGAS, interleukin-1, and interleukin-18 were co-localized.

CONCLUSIONS

These observations imply that along with the synthesis of interleukin-1 and interleukin-18, cGAS may be involved in the aetiology of apical periodontitis.

摘要

目的

环鸟苷酸-腺苷酸合酶(cGAS)作为一种关键的 DNA 传感器,已成为先天免疫和炎症的主要介质。人类根尖周炎尚未研究 cGAS 的存在。本研究旨在确定 cGAS 是否参与人类根尖周炎的病理过程。

方法

本研究采用 64 个人类根尖病变组织,包括 20 个根尖肉芽肿和 44 个根尖囊肿,同时使用健康牙龈(n=6)、牙髓(n=3)和根尖乳头(n=3)作为对照样本。采用免疫组织化学染色法检测根尖组织中 cGAS 的表达。采用 mRNA 测序和 qRT-PCR 检测与 DNA 感应信号相关的差异表达基因(DEGs)在根尖病变组织与健康对照组中的表达。采用免疫荧光标记法鉴定 cGAS、白细胞介素-1β和白细胞介素-18 的共表达。

结果

在根尖病变组织中发现 cGAS 的表达水平显著增加,根尖囊肿和根尖肉芽肿之间无显著差异。mRNA 测序分析和 qRT-PCR 鉴定出 cGAS 及其下游 DEGs 在根尖病变组织和健康对照组组织之间的差异表达mRNA。免疫荧光标记进一步显示 cGAS、白细胞介素-1 和白细胞介素-18 共定位。

结论

这些观察结果表明,cGAS 可能与白细胞介素-1 和白细胞介素-18 的合成一起参与根尖周炎的发病机制。

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