弹性蛋白稳定性增加导致沉积是肝纤维化不易逆转的特征，但调控弹性蛋白稳定性的机制尚不清楚。我们前期发现，促进弹性蛋白稳定性的组装蛋白Fibulin-1在纤维化形成及逆转中发挥着重要作用。据此我们提出假设以Fibulin-1为靶点可以调控弹性蛋白稳定性进而发挥抗纤维化作用。本研究首先在不同病因的肝纤维化样本中，利用组织学、分子生物学技术明确Fibulin-1的表达变化及与弹性蛋白的定位关系，并进一步检测Fibulin-1与病理分期的相关性。其次，分别在体外及体内建立不同干预模型，明确Fibulin-1对弹性蛋白结构和不可溶性成分的影响以及对肝纤维化的作用。最后，利用截短突变技术，初步揭示其调控弹性蛋白的结合位点。以期为临床多靶点抗纤维化治疗提供新的实验室依据。

Now it is considered that elastin deposition plays a key role in the irreversibility of liver fibrosis, which is induced by structural stabilization. However, the regulation mechanism on elastin stabilization in liver fibrosis is still unclear. Our previous work showed that the dynamic changes of Fibulin-1, which could promote the stabilization of elastin through regulation of assembly, was closely related to fibrosis progression and regression. Therefore, we hypothesized that Fibulin-1 inhibition could play anti-fibrotic roles through regulating the stabilization of elastin. In this study, we firstly will reveal the dynamic expression and histological co-localization of elastin and Fibulin-1 in different etiologies-induced liver fibrosis, as well as the relationship between Fibulin-1 levels and histological stages. Secondly, we utilized the vitro and vivo experiments to confirm the effects of Fibulin-1 on insoluble elastin and structure, furthermore on liver fibrosis. Finally, we applied the truncating mutations technology to explore the elastin-binding regions on Fibulin-1. This project intends to provide new insights for the role of Fibulin-1 in liver fibrosis and search for novel therapeutic strategies.