Quantitative Proteomic Analysis of Alcoholic Fatty Liver Biogenesis

描述（由申请人提供）：在西方世界，长期大量饮酒是导致肝脏疾病和死亡的主要原因。酒精性肝病（ALD）在临床和形态学上都有很好的特征，并分为疾病进展的三个主要阶段：1)脂肪肝，通常在戒酒的情况下是可逆的，2)酒精性肝炎或肝脏炎症，以及3)肝硬化或肝脏瘢痕形成。治疗ALD需要新的治疗工具。然而，为了开发这样的治疗方法，需要彻底了解酒精性肝损伤各个阶段的分子机制。高通量技术的最新发展使差异表达基因产物的全球分析成为现实。我们建议发展定量蛋白质组学策略，以确定促进ALD发展的分子机制。由于疾病进展的三个临床阶段的分子机制仍然知之甚少，我们将重点关注疾病的生物发生：1)确定ALD第1阶段，酒精性脂肪性肝病（AFLD）的分子机制，2)具体归因于使用的机制的解剖

DESCRIPTION (provided by applicant): Long-term heavy alcohol consumption is the leading cause of illness and death from liver disease in the Western world. Alcoholic liver disease (ALD) is well characterized clinically and morphologically and is described in three major stages of disease progression: 1) fatty liver, which is usually reversible with abstinence, 2) alcoholic hepatitis or liver inflammation, and 3) cirrhosis, or scarring of the liver. Novel therapeutic tools are needed for the treatment of ALD. However, to develop such therapies, a thorough understanding of the molecular mechanisms contributing to each stage of alcohol-induced liver injury is required. Recent developments in high-throughput technologies make the global profiling of differentially expressed gene products a reality. We propose to develop a quantitative proteomic strategy to identify the molecular mechanisms contributing to the development of ALD. Because the molecular mechanisms underlying each of the three clinical stages of disease progression are still poorly understood, we will focus on disease biogenesis: 1) the determination of the molecular mechanisms contributing to ALD Stage 1, alcoholic fatty liver disease (AFLD), 2) the dissection of the mechanisms specifically attributed to the use of alcohol by a comparative analysis with nonalcoholic fatty liver disease (NAFLD), and 3) the subsequent selection/characterization of protein biomarker candidates which can distinguish between alcoholic and nonalcoholic fatty liver and lead to the establishment of signature diagnostic panels for early disease progression.