日本血吸虫虫卵蛋白诱导肝星状细胞衰老的分子机制研究

项目名称： 日本血吸虫虫卵蛋白诱导肝星状细胞衰老的分子机制研究

项目编号： No.81471975

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： 段义农

作者单位： 南通大学

项目金额： 63万元

中文摘要： 活化的肝星状细胞衰老是肝纤维化逆转的重要机制之一。在日本血吸虫病肝纤维化逆转过程中，是否存在肝星状细胞衰老？其中肝星状细胞衰老及衰老肝星状细胞清除的机制是什么？目前尚未见报道。本项目的前期实验表明在晚期血吸虫病小鼠肝脏肉芽肿周围衰老的肝星状细胞增加，肝纤维化出现逆转。虫卵蛋白可以诱导活化的肝星状细胞衰老，信号转导相关分子p53和p21等表达上调。为了明确日本血吸虫虫卵蛋白对肝星状细胞衰老的作用及机制，本项目将运用肝星状细胞和p53-/-基因敲除小鼠肝纤维化模型等，观察日本血吸虫虫卵蛋白在体内外对肝星状细胞衰老的作用，筛选能诱导肝星状细胞衰老的虫卵蛋白分子，确定p53-p21-pRb信号通路是否参与促进肝星状细胞衰老，探讨衰老的肝星状细胞清除的分子机制。预期结果将为日本血吸虫病肝纤维化的防治提供新的潜在靶点。

中文关键词： 日本血吸虫；虫卵蛋白；肝星状细胞；衰老；信号转导

英文摘要： Senescence of activated hepatic stellate cells is considered to be one of the important mechanisms in reversing liver fibrosis. However, we wonder to know whether the senescence of activated hepatic stellate cells also plays a key role in reversing the liver fibrosis caused by the infection of Schistosoma japonicum. Furthermore, the mechanism of the senescence of activated hepatic stellate cells and the clearance of senescent stellate cells remains unclear. In our previous study, we found that the number of the senescent stellate cells around the hepatic egg gralunomas increased in the mice with advanced schistosomiasis, resulting in the reversion of liver fibrosis. And the egg proteins could induce the senescence of activated hepatic stellate cells and upregulate the expression of related proteins in signal transduction pathway, such as p53, p21. To define the effect of egg proteins on senescence of hepatic stellate cells and the mechanism of senescence of hepatic stellate cells, the hepatic stellate cell, p53-/- mouse model with liver fibrosis and so on could be utilized. We will observe the effect of egg proteins on senescence of hepatic stellate cells and screen the egg protein molecules which can induce senescence of hepatic stellate cells. And then we confirm whether the egg proteins induced-senescence of hepatic stellate cells is associated with p53-p21-pRb signaling pathway and explore the mechanism of the clearance of activated hepatic stellate cells through some experiments in vivo and in vitro. Desired outcomes will provide the potential target that could prevent liver fibrosis in the infection of Schistosoma japonicum.

英文关键词： Schistosoma japonicum;egg protein;hepatic stellate cell;senescence;signal transduction