Ding Shaojie, Mao Xinqi, Zhu Libo, Xu Xinxin, Chen Shuyi, Zou Gen, Xu Ping, Wang Jianzhang, Zhang Xinmei
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou Zhejiang, PR China, 310006; Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Hangzhou Zhejiang, PR China, 310006.
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou Zhejiang, PR China, 310006; Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Hangzhou Zhejiang, PR China, 310006.
Reprod Biomed Online. 2025 Aug;51(2):104796. doi: 10.1016/j.rbmo.2025.104796. Epub 2025 Jan 17.
Do mast cells play a role in the pathogenesis of endometriosis and, if so, what is the mechanism of action?
The study included 18 women with ovarian endometriosis and 13 women without endometriosis. Primary endometrial epithelial cells (EPC) were isolated and purified, and co-cultured with human mast cell line HMC-1.1 to explore the role and mechanisms of mast cells on epithelial mesenchymal transition (EMT) in EPC in vitro. Then, wild/c-kit mouse model of endometriosis was established by abdominal allogeneic endometrial transplantation in vivo. The number and location of mast cells in human/mouse endometrial tissue were determined by immunofluorescence staining. The expression levels of molecules related to CCL2, CCR4 and EMT were measured by quantitative reverse transcription polymerase chain reaction, Western blot and immunohistochemical staining analysis, respectively.
The number of infiltrated activated mast cells was positively correlated with EMT in human endometriotic lesions (CDH2, r = 0.53, P = 0.002; CDH1, r = -0.72, P < 0.001). Subsequently, mast cells promoted the migration and EMT of EPC through Mas-related G-protein-coupled receptor X2 (MRGPRX2)/C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor 4 (CCR4) signalling pathway in vitro. Finally, wild/c-kit mouse model of endometriosis showed that deficiency of mast cell activation suppressed the development of endometriosis via the restriction of EMT.
Mast cells are involved in the pathogenesis of endometriosis via MRGPRX2/CCL2/CCR4/EMT signals, thus providing a potential novel therapeutic approach for the treatment of endometriosis by targeting MRGPRX2/CCL2/CCR4 pathway.
肥大细胞在子宫内膜异位症的发病机制中是否起作用？如果起作用，其作用机制是什么？
该研究纳入了18例卵巢子宫内膜异位症患者和13例无子宫内膜异位症的女性。分离并纯化原代子宫内膜上皮细胞（EPC），并与人肥大细胞系HMC-1.1共培养，以体外探究肥大细胞对EPC上皮-间质转化（EMT）的作用及机制。然后，通过体内腹部同种异体子宫内膜移植建立野生型/c-kit子宫内膜异位症小鼠模型。通过免疫荧光染色确定人/小鼠子宫内膜组织中肥大细胞的数量和位置。分别通过定量逆转录聚合酶链反应、蛋白质免疫印迹和免疫组织化学染色分析检测与CCL2、CCR4和EMT相关分子的表达水平。
人子宫内膜异位病变中浸润的活化肥大细胞数量与EMT呈正相关（CDH2，r = 0.53，P = 0.002；CDH1，r = -0.72，P < 0.001）。随后，肥大细胞在体外通过Mas相关G蛋白偶联受体X2（MRGPRX2）/C-C基序趋化因子配体2（CCL2）/C-C趋化因子受体4（CCR4）信号通路促进EPC的迁移和EMT。最后，野生型/c-kit子宫内膜异位症小鼠模型显示，肥大细胞活化缺陷通过限制EMT抑制了子宫内膜异位症的发展。
肥大细胞通过MRGPRX2/CCL2/CCR4/EMT信号参与子宫内膜异位症的发病机制，从而为通过靶向MRGPRX2/CCL2/CCR4途径治疗子宫内膜异位症提供了一种潜在的新治疗方法。
