肝纤维化是慢性肝脏损伤终末期的共同病理阶段，目前尚缺乏针对性的干预方式，寻找肝纤维化的治疗新靶点意义重大。我们前期发现同源结构域相互作用蛋白激酶1（HIPK1）在纤维化小鼠肝脏及活化的肝星状细胞（HSC）中上调。体外过表达HIPK1促进HSC增殖以及肝纤维化相关基因表达，抑制HIPK1使HSC的增殖明显受到抑制。，我们推测HIPK1对肝纤维化具有调控作用，在HSC增殖、活化、迁移中发挥重要作用。本项目拟进一步结合细胞分子生物学手段及体内外功能挽救实验，阐明HIPK1通过形成HIPK1/HDAC7/MEF-2C复合体抑制MMP-10转录，介导肝纤维化的分子机制。同时在临床样本中验证探究HIPK1与临床肝纤维化程度的相关性。本项目将为以HIPK1为靶标开发抗肝纤维化药物提供理论实验依据。

Liver fibrosis is a common process of the end stage of chronic liver diseases, which still lacks targeted therapeutic methods. It is of great importance to explore the novel therapeutic targets for liver fibrosis. We found that Homeodomain Interacting Protein Kinase 1 (HIPK1) was up-regulated in fibrotic mice liver and activated hepatic stellate cells. Overexpression of HIPK1 led to hepatic stellate cell proliferation and fibrotic gene expression. In this project, we aim to investigate the roles of HIPK1 in liver fibrosis and its effects in proliferation, activation and migration of hepatic stellate cells. Cellular and molecular experiments and function rescue assays in vitro and in vivo will be further conducted to elucidate the molecular basis of HIPK1 in mediating liver fibrosis through forming HIPK1/HDAC7/MEF-2C complex and inhibiting MMP-10 transcription. The correlation between HIPK1 and the degree of clinical liver fibrosis will be confirmed in clinical samples. Our project will provide important evidence of inhibiting HIPK1 in the treatment of liver fibrosis.