除转录外,芳基烃受体还通过与 CaMKII 相互作用,在牙周炎中发挥保护作用。

IF 4.2 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of periodontology Pub Date : 2024-07-05 DOI:10.1002/JPER.24-0021
Xuwen Zeng, Meiting Feng, Jiawei Lu, Ruiling Wang, Li Deng, Yanan Yang, Lijun Luo
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引用次数: 0

摘要

背景:芳基烃受体(AhR)是一种细胞内模式识别受体,可以识别细菌色素。为了确定牙周炎的潜在治疗靶点,我们研究了 AhR 在牙周炎中的表达及其在牙周炎发病机制中的作用:首先,我们分析了人类牙周组织单细胞数据集中 AhR 的表达。定量聚合酶链反应(qPCR)、免疫荧光和免疫组化被用来验证 AhR 水平。随后,我们确定了髓细胞特异性 AhR 缺失小鼠(Lyz2-Cre+/- AhRfx/fx)结扎诱导牙周炎的表型,并利用 RNA 测序(RNA-seq)、qPCR、Western 印迹、免疫荧光和免疫组化等方法研究了 AhR 对牙周炎的影响及其机制。最后,我们确定了 AhR 激动剂 6-甲酰基吲哚并[3,2-b]咔唑(FICZ)对小鼠牙周炎的治疗效果,并在体外验证了 FICZ 对巨噬细胞极化的影响:结果:牙周炎患者的巨噬细胞中AhR表达增强。结果:牙周炎患者的巨噬细胞中 AhR 表达增强,巨噬细胞中 AhR 的缺失会加重结扎诱导的牙周炎并促进炎症反应。在 AhR 缺失的巨噬细胞中,钙/钙调蛋白激酶 II(CaMKII)磷酸化加速。抑制 CaMKII 磷酸化可改善 Lyz2-Cre+/- AhRfx/fx 小鼠的牙周炎。FICZ治疗可阻止牙槽骨流失并缓解牙周炎症。FICZ可减少M1巨噬细胞的极化,并在诱导M1巨噬细胞时促进M2巨噬细胞的极化:结论:AhR通过与CaMKII信号通路相互作用,协调巨噬细胞极化,从而在牙周炎的发病机制中发挥保护作用。
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Beyond transcription, aryl hydrocarbon receptor plays a protective role in periodontitis by interacting with CaMKII.

Background: The aryl hydrocarbon receptor (AhR) has been studied as an intracellular pattern recognition receptor that can identify bacterial pigments. To identify a potential therapeutic target for periodontitis, we investigated the expression of AhR in periodontitis and its role in the pathogenesis of periodontitis.

Methods: First, we analyzed AhR expression in a single-cell dataset from human periodontal tissue. Quantitative polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry were used to verify the AhR level. Later, we determined the phenotypes of ligature-induced periodontitis in myeloid-specific AhR-deficient mice (Lyz2-Cre+/- AhRfx/fx), after which RNA sequencing (RNA-seq), qPCR, Western blot, immunofluorescence, and immunohistochemistry were used to investigate the impacts of AhR on periodontitis and its mechanism. Finally, we determined the therapeutic effect of AhR agonist 6-Formylindolo[3,2-b]carbazole (FICZ) administration on murine periodontitis and verified the effects of FICZ on macrophage polarization in vitro.

Results: AhR expression was enhanced in macrophages from periodontitis patients. Deletion of AhR from macrophages aggravated ligature-induced periodontitis and promoted the inflammatory response. Calcium/calmodulin-stimulated protein kinase II (CaMKII) phosphorylation was accelerated in AhR-deficient macrophages. Inhibiting CaMKII phosphorylation ameliorated periodontitis in Lyz2-Cre+/- AhRfx/fx mice. FICZ treatment blocked alveolar bone loss and relieved periodontal inflammation. FICZ diminished M1 macrophage polarization and promoted M2 macrophage polarization upon M1 macrophage induction.

Conclusion: AhR played a protective role in the pathogenesis of periodontitis by orchestrating macrophage polarization via interacting with the CaMKII signaling pathway.

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来源期刊
Journal of periodontology
Journal of periodontology 医学-牙科与口腔外科
CiteScore
9.10
自引率
7.00%
发文量
290
审稿时长
3-8 weeks
期刊介绍: The Journal of Periodontology publishes articles relevant to the science and practice of periodontics and related areas.
期刊最新文献
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