ESR1经SDF-1/CXCR4轴介导的BMSCs归巢与分化在薄型子宫内膜发病中的作用及分子机制

项目名称： ESR1经SDF-1/CXCR4轴介导的BMSCs归巢与分化在薄型子宫内膜发病中的作用及分子机制

项目编号： No.81471417

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 袁瑞

作者单位： 重庆医科大学

项目金额： 70万元

中文摘要： 薄型子宫内膜是导致不孕不育的重要原因，其确切机制尚未阐明。雌激素受体α（ESR1）是配体依赖超家族成员。SDF-1/CXCR4是诱导干细胞归巢和迁移主要因子。课题组前期研究发现，1、ESR1基因多态性介导的ESR1蛋白表达低下与薄型子宫内膜发病间存在明显相关性2、薄型子宫内膜症干细胞相关指标显著低于正常水平3、雌激素处理BMSCs可上调归巢基因CXCR4表达，BMSCs迁移能力明显增强。结合文献提出ESR1在薄型子宫内膜发病过程中发挥了重要作用，其机制与ESR1表达下调影响BMSCs向子宫归巢及分化能力有关。本课题采用基因敲除与过表达技术研究BMSCs ESR1表达及同SDF-1/CXCR4轴的关系，探讨ESR1对BMSCs增殖、迁移与分化的影响，荧光活体成像等技术在体观察ESR1对BMSCs向子宫内膜归巢与分化的作用。研究结果将深化对薄型子宫内膜发病机制的认识，为临床治疗提供新思路。

中文关键词： 雌激素受体α；基质细胞衍生因子-1/趋化因子受体4；骨髓间充质干细胞；薄型子宫内膜

英文摘要： Thin endometrium is an important cause of infertility. The exact mechanism has not been elucidated. Estrogen receptor α (ESR1) belongs to the ligand-dependent transcriptional activity factor superfamily. Stromal cell-derived factor-1 (SDF-1)/Chemokine receptor 4 (CXCR4) plays a crucial role in stem cell mobilization and homing. our study had been observed 1. The pathogenesis of thin endometrium evidently related to the ESR1 gene polymorphism-induced ESR1 down regulation. 2. The stem cell related-markers in thin endometrium were dramatically decreased. 3. Estrogen treatment can up-regulate the expression of BMSCs homing gene CXCR4,the migration capability of BMSCs was significantly enhanced.As represented in some literatures, ESR1 down regulation resulted in the decrease of the homing capacity and differentiation of BMSCs, which might be responsible for the pathogenesis of the thin endometrium. In our project, we studied the expression of BMSCs ESR1 and its relationship with SDF-1/CXCR4 axis by gene knockdown and overexpression technologies, investigated the effect of ESR1 on BMSCs proliferation, migration and differentiation and observed the influence of ESR1 on the endometrial homing and differentiation of BMSCs in vivo via fluorescence imaging techniques. The results of our study throw light upon the pathogenesis of thin endometrium and provide new notions to clinical therapy.

英文关键词： ESR1;SDF-1/CXCR4;BMSCs;thin endometrium