Liu Xiaohan, Cheng Liqin, Huang Liuxuan, Li Mingyue, Shen Qingjun, Li Donghan, Dai Kailing, Fu Yanxia, Li Min, Yao Paul, Zeng Liqin
Department of Gynecology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Institute of Burns, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, China.
Front Endocrinol (Lausanne). 2025 Jun 24;16:1574938. doi: 10.3389/fendo.2025.1574938. eCollection 2025.
Endometriosis is a chronic inflammatory gynecological condition marked by the presence of tissue similar to the endometrium grows outside the uterus, often leading pelvic pain and infertility. This study explores how enhancer of zeste homolog 2 (EZH2) influences endometriosis, particularly through its interaction with estrogen receptors (ERs). We found that EZH2 reduces ERα expression, allowing ERβ to bind to the tumor necrosis factor α (TNFα) promoter and increase TNFα levels, fueling inflammation. In mice, the EZH2 inhibitor GSK343 reduced TNFα levels and endometriosis progression, similar to gene knockdown of ERβ or EZH2. In human samples, endometriotic tissue showed higher levels of EZH2 and ERβ and lower levels of ERα than in controls. Thus, EZH2 promotes TNFα-driven inflammation, contributing to endometriosis. Targeting EZH2, as with GSK343, could be a promising therapeutic strategy for endometriosis treatment.
子宫内膜异位症是一种慢性炎症性妇科疾病，其特征是子宫外存在类似子宫内膜的组织生长，常导致盆腔疼痛和不孕。本研究探讨了zeste同源物2（EZH2）增强子如何影响子宫内膜异位症，特别是通过其与雌激素受体（ERs）的相互作用。我们发现EZH2降低了ERα的表达，使ERβ能够结合肿瘤坏死因子α（TNFα）启动子并增加TNFα水平，从而加剧炎症。在小鼠中，EZH2抑制剂GSK343降低了TNFα水平和子宫内膜异位症的进展，类似于ERβ或EZH2的基因敲除。在人类样本中，与对照组相比，子宫内膜异位组织中EZH2和ERβ水平较高，而ERα水平较低。因此，EZH2促进TNFα驱动的炎症，导致子宫内膜异位症。像GSK343一样靶向EZH2可能是一种有前景的子宫内膜异位症治疗策略。
