部分上皮间质转化在矽肺纤维化中的作用机制

Partial epithelial-mesenchymal transition (partial EMT) is the critical phenomenon that when epithelial transformed to mesenchymal cells, the epithelial cell stay in the basement membrane. According to the recent studies, partial EMT may play an important role during the process, but the mechanism is not clear. In our previous work, silica induced partial EMT and increased the transcriptional factor Snail, which showed that Snail may be the key factor to regulate pulmonary fibrosis. We plan to explore the significance of Snail in silica-induced partial EMT in vitro and in vivo. In vitro, the mechanisms of Snail inducing partial EMT are going to be studied through the establishment of cell models of Snail gene overexpression and silence. We will detect the change about index of TGF-β、NF-κB to find the concrete mechanisms. In vivo, lentivirus disturbing Snail will be administered to transgene mice with pulmonary fibrosis induced by silica to investigate the regulation of partial EMT in the pulmonary fibrosis progression. Not only will this subject confirm our hypothesis and provide the new ideas to remedy the pulmonary fibrosis, but also has important public significance.

部分上皮间质转化（partial EMT）是上皮细胞向间质细胞转化却未离开基底膜的一种现象，最新研究提示partial EMT可能在组织纤维化中发挥重要作用，但机制不清。本课题组前期研究显示石英可诱导肺泡上皮细胞发生partial EMT，核转录因子Snail表达上调，提示Snail可能在partial EMT中发挥重要作用。本研究在此基础上拟利用共培养系统构建石英诱导的partial EMT细胞模型，通过沉默上皮细胞中的Snail基因，检测上皮细胞内TGF-β、NF-κB信号通路以及成纤维细胞相关指标的变化，研究partial EMT调控成纤维细胞活化的机制；体内实验通过使用转基因小鼠构建矽肺模型，给予RNAi干扰Snail的慢病毒进行处理，示踪特异标记的肺泡上皮细胞，探讨partial EMT在矽肺纤维化中的早期作用规律。该研究将为矽肺的早期治疗提供新思路，具有重要的公共卫生学意义。

部分上皮间质转化（partial EMT）是上皮细胞向间质细胞转化却未离开基底膜的一种现象，最新研究提示partial EMT可能在组织纤维化中发挥重要作用，但机制不清。本课题组研究发现石英可诱导肺泡上皮细胞发生partial EMT，核转录因子Snail表达上调，提示Snail可能在partial EMT中发挥重要作用。本研究在此基础上通过构建肺泡上皮细胞特异表达绿色荧光的转基因小鼠，分别建立转基因小鼠和野生型小鼠构建矽肺模型，给予RNAi干扰Snail的慢病毒进行处理，示踪特异标记的肺泡上皮细胞，探讨partial EMT在矽肺纤维化中的早期作用规律律，结果显示：Snail介导的partial EMT参与了石英诱导的小鼠肺纤维化过程，可能在矽肺纤维化中发挥重要作用；体外实验利用共培养系统，上室构建肺泡上皮细胞的partial EMT模型，下室培养肺成纤维细胞，通过沉默上皮细胞中的Snail基因，检测上室细胞partial EMT标志物以及下室成纤维细胞相关指标的变化，研究partial EMT调控成纤维细胞活化的机制，研究发现Snail介导的partial EMT能够引起肺内固有的成纤维细胞活化为肌成纤维细胞，这可能是partial EMT参与石英诱导小鼠肺纤维化的作用机制之一。该研究将为矽肺的早期治疗提供新思路，具有重要的公共卫生学意义。