肝再生过程中HSCs产生HGF，IL-6等细胞因子和调节ECM重塑，提供有利于肝细胞增殖的环境。ECM重塑是肝再生的必要步骤。表达于活化HSCs中的Hic-5参与了不同病理条件下对ECM的调控，Hic-5 敲除时减少胶原的合成，减轻鼠肝纤维化损伤。因此，Hic-5在调节HSCs参与ECM重塑中具有重要作用。目前尚未报道Hic-5调控肝再生的研究。课题组证实：Hic-5 KO提高小鼠PH后肝组织中Cyclin e1, Cyclin d1mRNA的水平，增加Ki-67的阳性细胞数等，促进肝再生。课题组以Hic-5 KO小鼠为研究工具，应用分子生物学技术，从组织学和细胞学层面探讨Hic-5在肝再生过程中对MKK4/JNK信号通路的影响及对ECM的调控，阐述Hic-5调控肝再生的具体机制。并以人细胞和小鼠为研究对象，明确Hic-5作为促肝再生治疗靶点的可行性，为丰富肝再生的机理和治疗提供有效证据。

In the process of liver regeneration, the activated hepatic stellate cells (HSCs) produce hepatic growth factor (HGF), Interleukin-6 (IL-6) and other factors, regulate the degradation and reconstruction of extracellular matrix (ECM) and provide a conducive environment for the proliferation of hepatocytes. Furthermore, the structure of ECM remodeling is a necessary step involving both degradation and reconstruction in the process of liver regeneration. Studies have shown that Hydrogen peroxide-inducible clone 5 (Hic-5) participates in regulating ECM under various pathological conditions. Hic-5 is also expressed in the human/mouse activated HSCs. Hic-5 deficiency alleviates liver fibrosis-induced liver injury by reducing the synthesis of collagen in mice. Therefore, Hic-5 plays an important role in regulating the HSCs involved in the degradation and reconstruction process of ECM. But there is no literature reporting on Hic-5’s regulating the liver regeneration. Our previous studies have confirmed that Hic-5 deficiency can increase the expression of Cyclin e1, Cyclin d1mRNA in the early phase after partial hepatectomy, raise the number of Ki-67 positive cells and the liver/body weight index as well as promote the liver regeneration. To further investigate the mechanism of Hic-5 in liver regeneration, our team will research on Hic-5 deficiency mice, apply the nucleic acid, protein analysis and histochemistry techniques to explore the Hic-5’s regulating MKK4/JNK signaling pathway and the degradation and reconstruction of ECM in the process of liver regeneration from the histological and cytological level. We will also describe the detailed mechanism of Hic-5 in regulating liver regeneration. Then, the human cell lines and wild type mices will be used as a research object to evaluate the feasibility of Hic-5 as a therapeutic target promoting liver regeneration. It will be provided with effective evidence for the mechanism of liver regeneration and a new therapeutic approach..