Kong Xiangyi, Xu Xiaofeng, Zhou Ling, Zhu Mengjing, Yao Shuang, Ding Yue, Liu Tao, Wang Yijin, Zhang Yan, Li Rong, Tang Xiaoqiu, Ling Jingxian, Wu Jun, Zhu Xianghong, Gu Yuanyuan, Zhou Huaijun
Department of Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.
Mol Ther Methods Clin Dev. 2020 Sep 28;19:295-306. doi: 10.1016/j.omtm.2020.09.013. eCollection 2020 Dec 11.
Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.
子宫内膜异位症是一种具有某些恶性特征的良性疾病。上皮-间质转化（EMT）参与子宫内膜异位症的发病机制。转移相关蛋白1（MTA1）通过促进EMT在各种癌症中发挥重要作用，但尚未有关于其在子宫内膜异位症中功能的研究。在本研究中，我们发现MTA1在子宫内膜异位症患者的异位内膜中高表达，且MTA1的表达与修订后的美国生育协会分期相关。MTA1通过诱导EMT促进子宫内膜间质细胞增殖、迁移和侵袭，而天然多酚白藜芦醇可抑制其促进作用和MTA1表达。此外，我们发现MTA1通过与ZEB2相互作用诱导EMT。在小鼠子宫内膜异位症模型中的研究结果进一步表明，MTA1和ZEB2在异位组织中上调，白藜芦醇可抑制异位病变的生长以及MTA1和ZEB2的表达。综上所述，我们证明MTA1是一种在子宫内膜异位症发病机制中通过与ZEB2相互作用促进EMT的蛋白，并且可能是白藜芦醇的作用靶点。
