Periostin蛋白在酒精性脂肪肝中的功能及机制研究

Periostin蛋白在炎症、纤维化和肿瘤等疾病中均发挥重要作用。我们已有的研究发现，Periostin在小鼠急慢性肝损伤组织和肝再生组织中高表达，敲除Periostin可明显减轻小鼠肝脏炎症和纤维化症状但抑制肝脏再生。我们的前期研究发现，Periostin在小鼠非酒精性脂肪肝组织中高表达，敲除Periostin可加重小鼠肝脏细胞脂滴累积等酒精性脂肪肝表型，但这与敲除Periostin在小鼠非酒精性脂肪肝中的表型相反，相关分子机制也不清楚。本项目将主要应用NIAAA酒精性脂肪肝小鼠模型和Periostin敲除小鼠等模型，研究Periostin在酒精性脂肪肝组织中表达上调及其调控肝细胞脂质代谢的分子机制，以阐明Periostin在酒精性脂肪肝中的功能及其作用机制，并比较Periostin在酒精性脂肪肝和非酒精性脂肪肝中的功能异同，为酒精性脂肪肝的诊断和治疗提供新的分子靶点。

Periostin plays an important role in inflammatory, fibrotic and tumor diseases. We have found that periostin is highly expressed in acute and chronic liver injury tissues and liver regeneration tissues in mice. Knockout of periostin can significantly reduce the symptoms of liver inflammation and fibrosis in mice, but inhibit liver regeneration after partial hepatectomy in mice. Our preliminary study found that periostin is highly expressed in non-alcoholic fatty liver tissues of mice. Knockout of periostin can aggravate the phenotype of alcoholic fatty liver such as lipid drop accumulation in liver cells of mice, which is contrary to the phenotype of in non-alcoholic fatty liver of periostin-knockout mice, but the related molecular mechanisms remain unclear. In this project, we will use NIAAA mouse model of alcoholic fatty liver and periostin-knockout mouse model to investigate the molecular mechanism of the up-regulation of periostin expression in alcoholic fatty liver tissue and its regulation of lipid metabolism in hepatocytes, so as to clarify the functions and mechanisms of periostin in alcoholic fatty liver, and compare the functions of periostin in alcoholic fatty liver and non-alcoholic fatty liver. This study will provide experimental evidence and a new molecular target for the diagnosis and treatment of alcoholic fatty liver disease.