Quantitative Proteomic Analysis of Alcoholic Fatty Liver Biogenesis

酒精性脂肪肝生物发生的定量蛋白质组学分析

• 批准号: 7085628
• 负责人: Christine C Wu
• 金额: $ 30.18万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-18 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085628
• 关键词: SDS polyacrylamide gel electrophoresis; alcoholic beverage consumption; alcoholic fatty liver; alcoholic hepatitis; alcoholic liver cirrhosis; alcoholism /alcohol abuse; biomarker; diagnosis design /evaluation; disease /disorder etiology; early diagnosis; electron microscopy; inflammation; laboratory rat; light microscopy; liver disorder diagnosis; method development; pathologic process; posttranslational modifications; protein structure function; proteomics; statistics /biometry; subcellular fractionation

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.

描述（由申请人提供）：在西方世界，长期大量饮酒是肝病导致疾病和死亡的主要原因。酒精性肝病 (ALD) 在临床和形态学上有明确的特征，并描述为疾病进展的三个主要阶段：1) 脂肪肝，通常可通过戒酒逆转，2) 酒精性肝炎或肝脏炎症，3) 肝硬化或疤痕肝脏的。治疗 ALD 需要新的治疗工具。然而，为了开发此类疗法，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得差异表达基因产物的全球分析成为现实。我们建议开发定量蛋白质组学策略来确定促进 ALD 发展的分子机制。由于疾病进展的三个临床阶段各自的分子机制仍知之甚少，因此我们将重点关注疾病的生物发生：1) 确定导致 ALD 第 1 阶段、酒精性脂肪肝 (AFLD) 的分子机制，2)对具体归因于使用的机制的剖析 通过与非酒精性脂肪性肝病 (NAFLD) 的比较分析来识别酒精，3) 随后选择/表征候选蛋白质生物标志物，这些候选物可以区分酒精性和非酒精性脂肪肝，并建立早期疾病进展的特征诊断组。