Y-box结合蛋白1对肝祖细胞介导的肝组织再生和肝纤维化形成的调节机制研究

肝祖细胞（HPC）作为慢性肝损伤时肝脏修复重要参与者，其活化增殖反应与纤维化发生和发展关系密切。Y-box结合蛋白1（YB-1）是一种可分泌多功能蛋白，前期研究显示其参与了多种组织、器官纤维化进程，且其发挥作用具有明显的细胞和组织特异性。本课题拟从细胞水平用siRNA干扰和质粒过表达方式下调和上调HPC与肝星状细胞（HSC）中YB-1，探索其对HPC增殖和分化以及HSC多种生物学功能的影响。并在YB-1转基因敲除鼠中构建急、慢性肝脏损伤修复模型，从体内角度阐明YB-1对肝脏损伤修复和纤维化形成影响。最后，观察不同病因慢性肝病中YB-1表达量和分布变化情况，阐明不同病因条件下YB-1与HPC以及HSC之间的关联。研究结果将进一步阐明YB-1在慢性肝脏损伤过程中肝脏修复和纤维化形成作用机制，从而有助于从YB-1这一新视角探索肝纤维化分子机制，为临床治疗肝纤维化提供新的理论和实验依据。

Hepatic progenitor cells（HPC） participant in liver regeneration during chronic liver injury, and its activation and proliferation is also closely related with liver fibrogenesis.Y-box binding protein 1 (YB-1) is a secreted multifunctional protein.Previously studies have shown that YB-1 was involved in the fibrogenesis of many tissues and organs with highly cell and tissue specificity.Our project intend to study the impact of down and up-regulated YB-1 by siRNA silencing and plasmid over-expression technologies on the proliferation,differentiation of HPC，and the activation, proliferation, migration, extracellular matrix synthesis of hepatic stellate cells（HSC）. Acute and chronic liver injury models in YB-1 transgenic knockout mice are constructed， and the effect of YB-1 on liver regeneration and fibrogenesis is clarified.Finally,we will investigat YB-1 expression in different causes of chronic liver disease, and clarify the association of YB-1 between HPC and HSC in different conditions.The results will further elucidate the mechanism of YB-1 in the process of liver regeneration and fibrogenesis in chronic liver injury, thus help to explore the molecular mechanism of liver fibrosis from a new perspective and provide new theoretical and experimental basis for clinical treatment of liver fibrosis.