我们前期研究发现苦参碱衍生物MASM能特异结合并稳定核糖体蛋白RPS5，抑制肝星状细胞（HSC）活化以及具有显著的抗肝纤维化作用。进一步研究表明RPS5通过对p-AKT去磷酸化调控HSC活化和肝纤维化，具有PP2C蛋白磷酸酶的功能。我们最近的研究提示GSK3β和ERK是 RPS5潜在的底物。本项目围绕RPS5具有磷酸酶的核糖体外功能的特性，在肝纤维化中起重要作用，进一步明确和筛选RPS5的底物及其参与调控的与肝纤维化相关的信号通路，同时研究 MASM抗肝纤维化的分子机制。通过转基因和肝组织特异基因剔除小鼠模型，进一步确证RPS5在肝纤维化中的作用和MASM抗肝纤维化的机制。研究结果可以更深入阐明RPS5的具体的作用底物和信号通路及其在肝纤维化发病中的机理，为肝纤维化的诊断和防治提供线索；同时进一步阐明MASM抗肝纤维化的分子机制，为其开发为肝纤维化治疗新药提供理论依据。

Our previous study have found that the matrine derivative MASM specifically bind to and stabilize the ribosomal protein RPS5, inhibition of hepatic stellate cells (HSC) activation and has significant role in anti liver fibrosis. Further study showed that RPS5 could modulate of HSC activation and hepatic fibrosis through dephosphorylating the Akt kinase and has the function of PP2C protein phosphatase. Our recent studies suggest that GSK3-beta and ERK are potential substrates. This project around the role of RPS5 with the phosphatase function in liver fibrosis intends to further clarify and screen RPS5 substrates and their participation in the regulation of signaling pathways associated with liver fibrosis, while research on molecular mechanism of liver fibrosis by MASM. The role of RPS5 in liver fibrosis and antifibrotic mechanism of MASM will be further confirmed by transgenic and liver specific knockout mice combining with liver fibrosis model. The results could clarify the substrates of RPS5 and the regulation of signaling pathways. The role of RPS5 would be further clarified in the pathogenesis of liver fibrosis, providing clues for the diagnosis and prevention of liver fibrosis. The antifibrotic mechanism of MASM would be further clarified, providing theoretical basis for its development and treatment of liver fibrosis.