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口腔扁平苔藓外周 T 淋巴细胞中失调的磷酯酶 D2/哺乳动物雷帕霉素靶蛋白/缺氧诱导因子 1α与疾病严重程度相关。

Deregulated phospholipase D2/mammalian target of rapamycin/hypoxia-inducible factor 1 alpha in peripheral T lymphocytes of oral lichen planus correlated with disease severity.

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, PR China.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, PR China; Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, PR China.

出版信息

Arch Oral Biol. 2019 Feb;98:26-31. doi: 10.1016/j.archoralbio.2018.11.003. Epub 2018 Nov 3.

Abstract

OBJECTIVE

Oral lichen planus (OLP) is a common T lymphocyte-mediated autoimmune disease of unknown etiology. The mammalian target of rapamycin (mTOR) can regulate proliferation, apoptosis, and autophagy of T lymphocytes, therefore impacting the T lymphocyte-mediated immunity. The present study was aimed to investigate the possible association between Akt/mTOR/4E-BP1 (eIF4E-binding protein 1) signaling, phospholipase D (PLD) and hypoxia-inducible factor 1 alpha (Hif-1α) in peripheral T lymphocytes of OLP and the correlation of their expression with the disease severity.

DESIGN

RAE (reticular, atrophic and erosive lesion) scores were used to assess the disease severity of OLP. Akt, mTOR, 4E-BP1, PLD1, PLD2 and Hif-1α expression in peripheral T lymphocytes were measured by using quantitative real-time polymerase chain reaction. Associations of Akt/mTOR/4E-BP1 expression with PLD1, PLD2 and Hif-1α expression were also assessed, respectively. Moreover, correlations of their expression with RAE scores were analyzed.

RESULTS

Expressions of mTOR, 4E-BP1, PLD2 and Hif-1α mRNA were significantly reduced in peripheral T lymphocytes of OLP patients, especially in erosive form. mTOR expression was positively correlated with PLD2 and Hif-1α expression in OLP. Moreover, mTOR, PLD2 and Hif-1α expression were negatively correlated with RAE scores, respectively.

CONCLUSIONS

Deregulated PLD2/mTOR/Hif-1α may contribute to the development of OLP and reflect the severity of the disease.

摘要

目的

口腔扁平苔藓(OLP)是一种常见的 T 淋巴细胞介导的自身免疫性疾病,病因不明。哺乳动物雷帕霉素靶蛋白(mTOR)可调节 T 淋巴细胞的增殖、凋亡和自噬,从而影响 T 淋巴细胞介导的免疫。本研究旨在探讨 T 淋巴细胞中 Akt/mTOR/4E-BP1(真核翻译起始因子 4E 结合蛋白 1)信号、磷脂酶 D(PLD)与缺氧诱导因子 1α(Hif-1α)之间的可能关联,及其表达与 OLP 疾病严重程度的相关性。

设计

采用网状、萎缩性和糜烂性病变(RAE)评分评估 OLP 的疾病严重程度。采用实时定量聚合酶链反应检测外周 T 淋巴细胞中 Akt、mTOR、4E-BP1、PLD1、PLD2 和 Hif-1α的表达。还分别评估了 Akt/mTOR/4E-BP1 表达与 PLD1、PLD2 和 Hif-1α表达的相关性。此外,还分析了它们的表达与 RAE 评分的相关性。

结果

OLP 患者外周 T 淋巴细胞中 mTOR、4E-BP1、PLD2 和 Hif-1α mRNA 的表达显著降低,尤其是在糜烂型中。mTOR 表达与 OLP 中 PLD2 和 Hif-1α 表达呈正相关。此外,mTOR、PLD2 和 Hif-1α 表达与 RAE 评分呈负相关。

结论

异常的 PLD2/mTOR/Hif-1α 可能有助于 OLP 的发展,并反映疾病的严重程度。

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