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牙周组织全转录组分析及免疫相关竞争性内源性 RNA 网络的构建。

Whole-transcriptome analysis of periodontal tissue and construction of immune-related competitive endogenous RNA network.

机构信息

Department of Periodontology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, School and Hospital of Stomatology, Peking University, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China.

出版信息

BMC Oral Health. 2022 Aug 31;22(1):370. doi: 10.1186/s12903-022-02401-0.

DOI:10.1186/s12903-022-02401-0
PMID:36045361
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9429583/
Abstract

BACKGROUND

In periodontitis, noncoding RNAs may play a regulatory role in the immune microenvironment through competitive endogenous RNA. We aimed to profile noncoding RNA expression and construct immune-related ceRNA network in periodontitis.

METHODS

Five inflamed periodontal tissue and five healthy gingivae were collected for whole-transcriptome sequencing. Differential gene, functional enrichment, and protein-protein interaction network analysis were performed to explore the function of differentially expressed genes. CIBERSORTx was used to analyze level of immune cell infiltration in the periodontal tissue. An immune-related competitive endogenous RNA network was constructed and expression of key regulators in the network was validated.

RESULTS

Compared with healthy gingiva, 200 mRNAs, 90 long noncoding RNAs, 65 microRNAs, and 518 circular RNAs were differentially expressed, and cell chemotaxis was significantly enhanced in inflamed periodontal tissue. Immune cell infiltration analysis showed that neutrophils, macrophages M1, T follicular helper cells, and naive B cells were significantly increased in periodontitis. Key regulators including JUN, FOS, THBS1, KLF2, WIF1, were identified and their expression was then validated.

CONCLUSION

We constructed an immune-related competitive endogenous RNA network in periodontal tissue, which provided new insights into immune homeostasis in periodontitis and laid a foundation for further study of noncoding RNAs. Key regulators in this network may be promising targets for future periodontitis treatment.

摘要

背景

在牙周炎中,非编码 RNA 可能通过竞争性内源 RNA 在免疫微环境中发挥调节作用。我们旨在分析牙周炎中非编码 RNA 的表达,并构建免疫相关的 ceRNA 网络。

方法

收集 5 例牙周炎组织和 5 例健康牙龈组织进行全转录组测序。进行差异基因、功能富集和蛋白质-蛋白质相互作用网络分析,以探讨差异表达基因的功能。采用 CIBERSORTx 分析牙周组织中免疫细胞浸润水平。构建免疫相关 ceRNA 网络,并验证网络中关键调节剂的表达。

结果

与健康牙龈相比,200 个 mRNAs、90 个长链非编码 RNA、65 个 microRNAs 和 518 个 circular RNAs 表达差异显著,炎症性牙周组织中细胞趋化性显著增强。免疫细胞浸润分析显示,牙周炎中中性粒细胞、M1 型巨噬细胞、滤泡辅助性 T 细胞和幼稚 B 细胞显著增加。鉴定出包括 JUN、FOS、THBS1、KLF2 和 WIF1 在内的关键调节剂,并验证了它们的表达。

结论

我们构建了牙周组织中的免疫相关 ceRNA 网络,为牙周炎中免疫稳态提供了新的见解,并为进一步研究非编码 RNA 奠定了基础。该网络中的关键调节剂可能是未来牙周炎治疗的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/5d829f62ff21/12903_2022_2401_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/d428e8ba56ba/12903_2022_2401_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/7674d6865ecf/12903_2022_2401_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/37b0e6d84bae/12903_2022_2401_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/3175f5fc6c37/12903_2022_2401_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/5d829f62ff21/12903_2022_2401_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/d428e8ba56ba/12903_2022_2401_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/7674d6865ecf/12903_2022_2401_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/37b0e6d84bae/12903_2022_2401_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/3175f5fc6c37/12903_2022_2401_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8316/9429583/5d829f62ff21/12903_2022_2401_Fig5_HTML.jpg

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J Periodontal Res. 2022 Jun;57(3):594-614. doi: 10.1111/jre.12989. Epub 2022 Apr 6.
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Profiling of plasma-derived exosomal RNA expression in patients with periodontitis: A pilot study.牙周炎患者血浆来源外泌体RNA表达谱分析:一项初步研究。
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Development of an immune-related lncRNA-miRNA-mRNA network based on competing endogenous RNA in periodontitis.
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Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity.人类口腔黏膜细胞图谱揭示了调节组织免疫的基质-中性粒细胞轴。
Cell. 2021 Jul 22;184(15):4090-4104.e15. doi: 10.1016/j.cell.2021.05.013. Epub 2021 Jun 14.
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Periodontitis activates the NLRP3 inflammasome in serum and saliva.牙周炎会激活血清和唾液中的NLRP3炎性小体。
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