GOLM1介导骨桥蛋白和胆固醇相互作用促进胆囊胆固醇结石形成的机制研究

围绕胆固醇代谢调控对胆囊胆固醇结石形成机制进行深入研究具有重大意义。申请人前期系列工作发现骨桥蛋白（osteopontin,OPN）可调控胆固醇代谢影响胆囊胆固醇结石形成，胆固醇代谢也可影响OPN的表达和作用，但两者相互作用的确切机制尚不明确。结合前期工作基础和文献报道，我们提出科学假设：OPN和胆固醇相互作用促进胆囊胆固醇结石形成；高尔基体蛋白1（Golgi Membrane Protein 1,GOLM1）既可调控OPN的成熟和分泌，又受到细胞内胆固醇水平的影响，可能是介导OPN和胆固醇相互作用的重要调控因子。本课题将从细胞水平研究OPN与胆固醇之间存在交叉对话(Crosstalk)，相互影响；研究GOLM1是介导该相互作用的重要调控因子，探讨其调控机制；并从动物和人体组织水平验证其在胆囊胆固醇结石形成中的作用和机制。本研究有望为防治胆囊胆固醇结石提供新的理论基础和治疗靶点。

The regulation of cholesterol metabolism is of great significance in the process of cholesterol gallstone formation. Our previous work found that osteopontin (OPN) played an important role in the formation of cholesterol gallstones by involving in cholesterol metabolism. In turn, cholesterol could affect the function and expression of OPN. But the exact mechanism is not clear. Based on our previous work and other published literature, we propose a hypothesis that the interaction between OPN and cholesterol promotes the formation of cholesterol gallstones. An important protein, Golgi Membrane Protein 1 (GOLM1) can both regulate the maturation and secretion of OPN and be affected by cell internal cholesterol levels, which may make it a critical regulator in cholesterol gallstone formation. This study will research into the crosstalk between OPN and cholesterol at the cellular level, the role of GOLM1 as an important regulator mediating this interaction and verifying its role in cholesterol gallstone formation at the animal and human levels. In the end, the study is expected to provide a new theoretical basis and therapeutic targets for the prevention and treatment of cholesterol gallstone.