RON介导的上皮-间质转换在子宫内膜异位症发生发展中的作用机制研究

Endometriosis is a common gynecologic disease in women of reproductive age, which severely impacts on women's physical and mental health. The causes of endometriosis remain unclear, it results in a lack of clinical prevention and treatment of endometriosis. Our preliminary results showed that the level of the recepteur d’origine nantais (RON) expression in ectopic endometrium was significantly higher than that in matched eutopic endometrium and normal endometrium. Many studies have shown that the epithelial-mesenchymal transition (EMT) of endometriotic cells plays a key role in the pathogenesis of endometriosis, and the process of EMT is directly regulated by RON. Therefore, we put forward an innovative hypothesis that the EMT mechanism of endometriotic cells mediated by RON is the important matters in the pathogenesis of endometriosis. In the present project, we will perform the research in clinical observations, animal studies and in-vitro studies to clarify the mechanism of EMT mediated by RON in the pathogenesis of endometriosis. We will also give a full explanation of the pathophysiological mechanisms of the EMT of endometriotic cells mediated by RON involved in the pathogenesis of endometriosis. This research will provide a new theoretical basis and reliable scientific basis to prevention and cure endometriosis.

子宫内膜异位症（内异症）是严重影响妇女身心健康的一种妇科常见病，其发病机制不清，导致临床预防与治疗对策缺乏。我们前期研究发现，与正常子宫内膜相比，内异症病灶RON（recepteur d’origine nantais，RON）蛋白表达显著上调。提示，RON与内异症发病有关。研究发现，RON直接调节细胞上皮-间质转换（epithelial-mesenchymal transition，EMT）的全过程，而异位内膜细胞EMT是内异症发生发展的最关键环节。因此，我们创新性地提出，内异症发生发展过程中异位内膜细胞上RON介导的异位内膜细胞EMT过程可能是内异症发生发展的重要环节。本项目从临床观察、动物实验及体外实验多方面深入研究。通过阐明RON介导的异位内膜细胞EMT在内异症发生发展中的作用机制，证实RON是内异症异位内膜细胞EMT的关键调节因子，为相关疾病的防治提供新的理论基础和可靠科学依据。

子宫内膜异位是一种良性，慢性炎症性疾病，通常发生在育龄妇女中。子宫内膜上皮细胞的上皮-间质转化（EMT）在子宫内膜异位症的发展中起着重要作用。据报道，受体酪氨酸激酶RON可以促进肿瘤的EMT从而在肿瘤发证发展中发挥作用。然而，尚不清楚RON是否在子宫内膜异位症的发展中介导EMT。在此研究中，我们发现RON激活可以增强子宫内膜上皮细胞的迁移和侵袭能力，改变细胞形态，并降低E-cadherin的表达并增加N-cadherin的表达。 抑制RON表达或使用其抑制剂可以抑制子宫内膜上皮细胞的迁移和侵袭。我们的研究还表明，RON通过蛋白激酶B（Akt）和有丝分裂原激活的蛋白激酶（MAPK）途径在子宫内膜上皮细胞中发挥了作用。用RON抑制剂治疗可以减少子宫内膜异位症小鼠模型中异位病变的数量，并调节子宫内膜异位病变中EMT标记的表达。这些数据表明RON通过促进子宫内膜上皮细胞的EMT促进了子宫内膜异位症的发展。因此，RON可能是子宫内膜异位症的新治疗靶点。