Analysis of the role of Four and a half LIM domains protein 2 (FHL2) in hepatic lipid metabolisms in non-alcoholic fatty liver disease (NAFLD)

四个半LIM结构域蛋白2（FHL2）在非酒精性脂肪性肝病（NAFLD）肝脂代谢中的作用分析

• 批准号: 496131177
• 负责人: Professor Dr. Claus Hellerbrand
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/496131177?language=en
• 关键词: Analysis; role; Four; half; LIM

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Hepatic steatosis is the first step and driving force of the NAFLD-pathology. Therefore, a comprehensive understanding of the molecular mechanisms leading to the accumulation of intrahepatic lipids is critically needed to support the development of effective forms of treatments for NAFLD, which are so far missing but highly needed. FHL2 is the second member of the "four-and-a-half LIM-domain" protein-family. FHL2 is ubiquitously expressed and is involved in the regulation of various biological mechanisms in health and disease. FHL2 lacks direct DNA binding activities but interacts with numerous proteins including transcription factors, and herewith, acts as transcriptional coactivator or corepressor. Our preliminary work indicates that enhanced FHL2 expression in hepatocytes promotes liver steatosis in NAFLD. The aims of this project are to characterize the molecular mechanisms by which FHL2 affects hepatic steatosis in preclinical models and to validate the findings in clinical samples of NAFLD-patients. The overall goal is the identification of new therapeutic targets for the inhibition of the development and progression of NAFLD.

非酒精性脂肪性肝病（NAFLD）是全球最常见的肝病。肝脏脂肪变性是NAFLD病理的第一步和驱动力。因此，迫切需要全面了解导致肝内脂质积聚的分子机制，以支持开发NAFLD的有效治疗形式，这是迄今为止缺失但非常需要的。FHL2是“四个半LIM结构域”蛋白家族的第二个成员。FHL2广泛表达，并参与健康和疾病中各种生物学机制的调节。FHL2缺乏直接的DNA结合活性，但与包括转录因子在内的许多蛋白质相互作用，并因此充当转录辅激活因子或辅阻遏因子。我们的初步工作表明，肝细胞中FHL2表达的增强促进了NAFLD中的肝脏脂肪变性。该项目的目的是表征FHL2在临床前模型中影响肝脂肪变性的分子机制，并验证NAFLD患者临床样本中的发现。总体目标是确定抑制NAFLD发展和进展的新治疗靶点。