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牙周膜干细胞来源的外泌体 microRNA-155-5p 通过靶向沉默信息调节因子 1 调控慢性牙周炎中的 Th17/Treg 平衡。

Exosomal microRNA-155-5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin-1 in chronic periodontitis.

机构信息

Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.

Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

J Cell Physiol. 2019 Nov;234(11):20662-20674. doi: 10.1002/jcp.28671. Epub 2019 Apr 23.

Abstract

The mechanism of local inflammation and systemic injury in chronic periodontitis is complicated, in which and exosomes play an important role. In our study, we found that T helper cell 17 (Th17)/regulatory T cell (Treg) balance is destabilized in the peripheral blood of patients with periodontitis, with upregulated Th17 or downregulated Treg, respectively. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment of chronic periodontitis. The exosomes were extracted from periodontal ligament stem cells (PDLSCs) in LPS-induced periodontitis environment, which inversely effected on CD4+ T cells under normal and inflammatory conditions. Furthermore, compared with exosomes from normal PDLSCs, lower expression of microRNA-155-5p (miR-155-5p) and higher expression of Sirtuin-1 (SIRT1) were observed in exosomes from LPS-stimulated PDLSCs. Exosomes from PDLSCs alleviated inflammatory microenvironment through Th17/Treg/miR-155-5p/SIRT1 regulatory network. This study aimed to find the "switching" factors that affected the further deterioration of periodontitis to maximally control the multiple downstream damage signal factors to further understand periodontitis and find new targets for its treatment.

摘要

慢性牙周炎中局部炎症和全身损伤的机制很复杂,其中外泌体起着重要作用。在我们的研究中,我们发现牙周炎患者外周血中的辅助性 T 细胞 17(Th17)/调节性 T 细胞(Treg)平衡被打破,分别表现为 Th17 上调或 Treg 下调。牙龈卟啉单胞菌脂多糖(LPS)被用来模拟慢性牙周炎的炎症微环境。从 LPS 诱导的牙周炎环境中的牙周韧带干细胞(PDLSCs)中提取外泌体,在正常和炎症条件下对 CD4+T 细胞产生相反的影响。此外,与来自正常 PDLSCs 的外泌体相比,LPS 刺激的 PDLSCs 中的外泌体中 microRNA-155-5p(miR-155-5p)的表达降低,Sirtuin-1(SIRT1)的表达升高。PDLSCs 的外泌体通过 Th17/Treg/miR-155-5p/SIRT1 调节网络缓解炎症微环境。本研究旨在寻找影响牙周炎进一步恶化的“开关”因素,最大限度地控制多个下游损伤信号因素,以进一步了解牙周炎并为其治疗寻找新的靶点。

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