Department of Gynecology, Zhangjiagang First People's Hospital, The Zhangjiagang Affiliated Hospital of Soochow University, Zhangjiagang, China.
Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4509-4515.
Oxidative stress caused by reactive oxygen species (ROS) plays an important role in the pathogenesis of endometriosis. The gene AT-rich interactive domain 1A (ARID1A), is frequently down regulated and inactivated in endometriosis. This report is focused on the molecular mechanism of the correlation between oxidative stress and ARID1A gene expression in endometrial cell oxidative damage model.
In this study, the ARID1A gene expression level and its promoter methylation level were detected in 30 endometriosis and normal tissues. The primary endometrial cell was co-cultured with H2O2. Then, MDA and Gpx level were used to test the ROS level, RT-PCR was employed to detect the expression level of ARID1A. At last, the ARID1A gene promoter methylation level was detected by methylation-specific PCR (MSP). Finally, the expression level of DNMT1 was detected by both RT-PCR and Western blot.
The expression level of ARID1A gene was down regulated in endometriosis compared with normal tissues. The low expression level of ARID1A gene was associated with its promoter hyper-methylation. In H2O2 simulated endometrial cells, ARID1A gene expression level was decreased. Finally, ROS regulated ARID1A gene expression by changing the methylation level of ARID1A gene promoter. Finally, both the mRNA level and protein level of DNMT1 increased in H2O2 simulated endometrial cells.
In endometriosis, the down-regulated ofARID1A gene was highly correlated with its promoter hyper-methylation. ROS decreased the expression level of ARID1A gene via regulating methylation of its promoter which contributing to the understanding of the pathogenesis of endometriosis. The possible mechanism of ARID1A gene promoter hyper-methylation is ROS up-regulated DNMT1gene expression.
活性氧（ROS）引起的氧化应激在子宫内膜异位症的发病机制中起重要作用。富含 AT 的相互作用结构域 1A（ARID1A）基因在子宫内膜异位症中经常下调和失活。本报告重点介绍了氧化应激与子宫内膜细胞氧化损伤模型中 ARID1A 基因表达之间相关性的分子机制。
在这项研究中，检测了 30 例子宫内膜异位症和正常组织中 ARID1A 基因的表达水平及其启动子甲基化水平。将原代子宫内膜细胞与 H2O2 共培养。然后，使用 MDA 和 Gpx 水平检测 ROS 水平，使用 RT-PCR 检测 ARID1A 的表达水平。最后，通过甲基化特异性 PCR（MSP）检测 ARID1A 基因启动子的甲基化水平。最后，通过 RT-PCR 和 Western blot 检测 DNMT1 的表达水平。
与正常组织相比，子宫内膜异位症中 ARID1A 基因的表达水平下调。ARID1A 基因低表达与启动子高甲基化有关。在 H2O2 模拟的子宫内膜细胞中，ARID1A 基因表达水平降低。最后，ROS 通过改变 ARID1A 基因启动子的甲基化水平调节 ARID1A 基因的表达。最后，在 H2O2 模拟的子宫内膜细胞中，DNMT1 的 mRNA 水平和蛋白水平均增加。
在子宫内膜异位症中，ARID1A 基因下调与启动子高甲基化高度相关。ROS 通过调节其启动子的甲基化降低 ARID1A 基因的表达水平，有助于了解子宫内膜异位症的发病机制。ARID1A 基因启动子高甲基化的可能机制是 ROS 上调 DNMT1 基因表达。
