Wnt/β-catenin信号通路对子宫内膜异位症SP细胞的调控研究

Endometriosis is one of the frequently observed diseases that adversely affect women of reproductive age. While its etiology and pathogenesis remain unclear, recent studies suggest that endometrial stem cells can be associated with this disease. The SP cell as an important endometrial stem cell is capable of the expression of VEGF. By means of flow cytometry, our group isolated SP cells from the eutopic endometrium of endometriosis patients, and the isolated SP cells cultured in vitro could form clone and demonstrated characteristics of typical stem cell. Meanwhile, Wnt/β-catenin signaling pathway is abnormally activated in endometriosis and can upgrade the expression of VEGF in intestinal tumor. Based on this, the project expects to employ immunocytochemistry, FACS, Western Blot, RT-PCR, cell proliferation assays, animal model and ELISA to study the effect of Wnt/β-catenin signaling pathway on the proliferation and differentiation of SP cell, as well as its association with angiogenesis in endometriosis. We expect an initial identification of the role of SP cell in the incidence of endometriosis. The study will provide experimental evidence for the stem cell theory of endometriosis, and also shed light on the diagnosis and treatment of endometriosis (such as targeted therapy).

子宫内膜异位症严重影响育龄妇女的生殖功能和身心健康，但其发病机制至今不明，有学者认为内膜干细胞可能与发病相关，SP细胞是子宫内膜重要的干细胞，且可表达VEGF等血管生成因子。本课题组前期通过流式细胞在内异症在位内膜分离出了SP细胞，体外培养形成克隆，呈现典型的干细胞特征。同时，Wnt/β-catenin信号通路在内异症中被异常激活，在肠道肿瘤形成过程中该通路可上调VEGF的表达。基于此，本项目拟采用免疫组化、免疫细胞化学染色、 FACS、Western Blot、RT-PCR、细胞增殖迁移实验及动物实验、ELISA等实验方法研究，观察Wnt/β-catenin信号通路对SP细胞增殖及分化的调控作用，以及SP细胞在内异症血管生成中的作用，从而初步阐明SP细胞在内异症发生中的作用。该研究将为内异症的干细胞学说提供实验 依据，也为内异症的诊治（如靶向治疗）提供新思路。