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叉头框蛋白 P3 通过调控 microRNA-146a 控制口腔扁平苔藓的进展。

Forkhead box p3 controls progression of oral lichen planus by regulating microRNA-146a.

机构信息

Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

J Cell Biochem. 2018 Nov;119(11):8862-8871. doi: 10.1002/jcb.27139. Epub 2018 Aug 20.

DOI:10.1002/jcb.27139
PMID:30125971
Abstract

Oral lichen planus (OLP) is a severe T cell-mediated disorder of the mucosa, which causes chronic inflammation. Forkhead box P3 (Foxp3) regulates the immune response and plays an important role in immunological diseases. The current study aimed to determine the role of Foxp3 and microRNA (miR)-146a in OLP. Western blot analysis and a quantitative real-time polymerase chain reaction assay showed that the expression of Foxp3 and miR-146a was upregulated in OLP tissues and in lipopolysaccharide (LPS)-incubated HaCaT cells, compared with controls. Foxp3 inhibition significantly decreased miR-146a expression, ameliorated LPS stimulation by decreased cell proliferation, and apoptosis in LPS-incubated HaCaT cells as compared with the LPS group. Cotransfection of Foxp3 small interfering RNA and miR-146a mimics elevated cell proliferation and apoptosis compared with the Foxp3 small interfering RNA group. In addition, miR-146a overexpression upregulated, whereas miR-146a inhibition downregulated, the proliferation and apoptosis of LPS-incubated HaCaT cells. The target gene of miR--146a, tumor necrosis factor receptor-associated factor 6 (TRAF6), was predicted by bioinformatics software and identified by the luciferase reporter assay. Furthermore, Foxp3/miR-146a elevated T regulatory cells and regulated TRAF6 expression in CD4 T cells that were isolated from peripheral blood of patients with OLP. In conclusion, our study suggests that Foxp3 and miR-146a regulate the progression of OLP by negatively regulating TRAF6, which may provide a promising therapeutic target for OLP treatment.

摘要

口腔扁平苔藓(OLP)是一种严重的 T 细胞介导的黏膜疾病,可引起慢性炎症。叉头框 P3(Foxp3)调节免疫反应,在免疫性疾病中发挥重要作用。本研究旨在探讨 Foxp3 和 microRNA(miR)-146a 在 OLP 中的作用。Western blot 分析和实时定量聚合酶链反应检测显示,与对照组相比,OLP 组织和脂多糖(LPS)孵育的 HaCaT 细胞中 Foxp3 和 miR-146a 的表达上调。与 LPS 组相比,Foxp3 抑制可显著降低 miR-146a 的表达,改善 LPS 刺激导致的 HaCaT 细胞增殖减少和凋亡。与 Foxp3 小干扰 RNA 组相比,Foxp3 小干扰 RNA 和 miR-146a 模拟物的共转染可升高细胞增殖和凋亡。此外,miR-146a 过表达可上调 LPS 孵育的 HaCaT 细胞的增殖和凋亡,而 miR-146a 抑制可下调其增殖和凋亡。miR-146a 的靶基因肿瘤坏死因子受体相关因子 6(TRAF6)通过生物信息学软件预测,并通过荧光素酶报告基因检测鉴定。此外,Foxp3/miR-146a 通过上调调节性 T 细胞并调节外周血 OLP 患者 CD4 T 细胞中 TRAF6 的表达来调节 OLP 的进展。综上所述,本研究表明 Foxp3 和 miR-146a 通过负调控 TRAF6 调节 OLP 的进展,这可能为 OLP 的治疗提供一个有前途的治疗靶点。

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