Zhang Zhimin, Yuan Yi, He Lian, Yao Xiaoguang, Chen Jingwei
Department of Obstetrics, The Fourth Hospital of Shijiazhuang City, Shijiazhuang, Hebei 050011, P.R. China.
Department of Obstetrics and Gynecology, Zhejiang Hospital, Hangzhou, Zhejiang 310030, P.R. China.
Exp Ther Med. 2020 Oct;20(4):3269-3277. doi: 10.3892/etm.2020.9071. Epub 2020 Jul 29.
Endometriosis (EM) is a common disease in women; however, the signaling pathways and related genes underlying the mechanisms of EM remain unclear. The present study aimed to investigate the role of angiotensin II receptor type 1 (AGTR1) in the pathogenesis of EM. Human EM tissues were collected, and the expression levels of AGTR1 and NF-κB in the tissues were analyzed using immunochemistry and western blotting, while the estrogen levels in the EM tissues were determined by ELISA. human endometrial stromal cells were used to investigate the expression levels of AGTR1 following exposure to estrogen; the interaction between AGTR1 and NF-κB was determined using reverse transcription-quantitative PCR and western blotting; and the effects of AGTR1 on cell proliferation, as well as the apoptotic and migratory abilities of the cells were evaluated using WST-1 assays, wound healing assays and flow cytometry, respectively. It was observed that both the expression levels of AGTR1 and the activity of NF-κB were increased in human EM tissues and stromal cells, and this activation of AGTR1 subsequently increased the activity of NF-κB. Moreover, estrogen was found to regulate the expression levels of AGTR1 in stromal cells. The activation of AGTR1 was demonstrated to promote cell proliferation and migration, in addition to preventing cells from undergoing apoptosis. In conclusion, the present study suggested that the increased activity of the AGTR1-NF-κB axis following the decreased exposure to estrogen may be important for the pathogenesis of EM. In addition, AGTR1 may be a potential therapeutic target for the treatment of EM.
子宫内膜异位症（EM）是女性的一种常见疾病；然而，EM发病机制背后的信号通路和相关基因仍不清楚。本研究旨在探讨1型血管紧张素II受体（AGTR1）在EM发病机制中的作用。收集人EM组织，采用免疫化学和蛋白质印迹法分析组织中AGTR1和NF-κB的表达水平，同时通过酶联免疫吸附测定法测定EM组织中的雌激素水平。用人子宫内膜基质细胞研究暴露于雌激素后AGTR1的表达水平；采用逆转录定量PCR和蛋白质印迹法确定AGTR1与NF-κB之间的相互作用；分别采用WST-1检测、伤口愈合检测和流式细胞术评估AGTR1对细胞增殖以及细胞凋亡和迁移能力的影响。结果观察到，人EM组织和基质细胞中AGTR1的表达水平和NF-κB的活性均升高，并且AGTR1的这种激活随后增加了NF-κB的活性。此外，发现雌激素可调节基质细胞中AGTR1的表达水平。已证明AGTR1的激活除了可防止细胞凋亡外，还能促进细胞增殖和迁移。总之，本研究表明，雌激素暴露减少后AGTR1-NF-κB轴活性增加可能对EM的发病机制具有重要意义。此外，AGTR1可能是治疗EM的一个潜在治疗靶点。
