砷诱导的炎性因子通过TGF-β/Smad和microRNA调控膀胱上皮细胞EMT的机制研究

项目名称： 砷诱导的炎性因子通过TGF-β/Smad和microRNA调控膀胱上皮细胞EMT的机制研究

项目编号： No.81502834

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王菲

作者单位： 中国医科大学

项目金额： 18万元

中文摘要： 砷是已知的人类致癌物，但目前砷致膀胱癌的机制仍不清楚。我们实验组前期研究发现砷能够诱导人膀胱上皮细胞COX-2、PGE2、TNF-α等炎性因子表达增加。炎性微环境能促进细胞增殖、生存、转移和血管发生。上皮细胞间充质转化（Epithelial-mesenchymal transition，EMT）是这一过程中的重要事件，本项目推测EMT是连结砷诱导的炎症反应与膀胱上皮细胞恶性转化的重要桥梁。因此，本研究通过体外细胞实验和大鼠体内实验检测炎性因子与EMT转化相关因子、TGF-β/smad信号通路和相应的micRNAs之间相互作用，以EMT作为炎性反应和细胞恶性转化的结合点，探讨炎性因子调控砷诱导的膀胱上皮细胞EMT和恶性转化的机制，对砷致膀胱癌的机制研究有重要的理论意义。此外，本项目拟观察脱离亚慢性砷暴露环境的大鼠膀胱上皮细胞炎性因子的变化和EMT的逆转情况，为砷致膀胱癌的预防提供科学数据。

中文关键词： 砷；上皮间质转化；炎性因子；TGF-β/Smad；microRNA

英文摘要： Arsenic is a known human carcinogen, the mechanism of bladder cancer induced by arsenic is still unclear. We have found that arsenic increased the expression of some inflammatory cytokines (COX-2, PGE2, IL-8, TNF-α). It is known that inflammatory microenvironment could promote cell proliferation, survival, metastasis, angiogenesis and so on. Epithelial-mesenchymal transition (EMT) is an important event in the process. This project speculates that EMT play an interactive role between inflammation and malignant transformation induced by arsenic in uroepithelial cells. This project will study the interaction between inflammatory cytokines (COX-2, IL-1β, IL-6, IL-8, TNF-α) and EMT-related factors (SNAIL, TWIST1/TWIST2, ZEB1/ZEB2, E-cadherin, N-cadherin, Vimentin, MMP-9), TGF-β/smad pathway and miRNAs in vivo and in vitro. . The mechanism study of arsenic-induced inflammatory cytokines regulated EMT in uroepithelial cells will help us to reveal the molecular mechanism of bladder cancer induced by arsenic. In addition, our project will detect that EMT reversion is occured in rat uroepithelial cells after rats break away from DMA exposure. Based on the early inflammatory reaction of bladder, it provide a feasible project for bladder cancer prevention.

英文关键词： arsenic;EMT;inflammatory cytokines;TGF-β/Smad;microRNA