HBV介导S100A9/NLRP3/Caspase-1信号活化在肝纤维化发病机理中的作用及其临床价值

S100 protein family is a novel kind of damage-associated molecular patterns that could regulate infection-related inflammatory and immune responses. Our preliminary data indicate that S100A9, a member of S100s, was regulated by HBV and involved in activation of a key cell line (HSCs) in liver fibrosis. However, the exact molecular mechanism is still unknown. NLRP3/Caspase-1-dependent pyroptosis is a newly identified cell inflammatory death pattern, yet its role in HBV-related liver fibrosis remains uncertain.Still, it is unclear whether S100A9 facilitates HBV-related liver fibrosis by activating NLRP3/Caspase-1-dependent hepatocyte pyroptosis. Based on our preliminary data, we will illustrate the role of NLRP3/Caspase-1-dependent hepatocyte pyroptosis regulated by S100A9 in HBV-related liver fibrosis and its clinical significance by clinical sample analysis, cell-based assay and animal experiments. Our proposed study will provide theoretical and experimental basis for revealing the pathogenesis of in HBV-related liver fibrosis.

S100家族是一类新型的损伤相关模式分子，在感染性炎症免疫反应中发挥重要作用。我们前期发现该家族成员S100A9受HBV的调控，与肝纤维化关键细胞(肝星状细胞)的活化有关，但具体机制不明。NLRP3/Caspase-1信号依赖的细胞焦亡是新近发现的一种炎性细胞死亡，其在HBV相关肝纤维化中的作用尚未完全阐明。那么，受HBV调控的S100A9是否可通过调控NLRP3/Caspase-1信号依赖的肝细胞焦亡，参与活化肝星状细胞最终诱发肝纤维化发生，值得我们深入挖掘。本项目拟在前期基础上，将NLRP3/Caspase-1信号依赖的肝细胞焦亡作为切入点，分别从临床、细胞及动物层面系统研究S100A9对NLRP3/Caspase-1信号依赖的肝细胞焦亡的调控及其在HBV相关肝纤维化中的作用及临床意义。本项目将为HBV相关肝纤维化的发病机制提供理论基础和实验依据。

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