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: 8231792
• 负责人: Christine C Wu
• 金额: $ 25.56万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8231792
• 关键词: Quantitative; Proteomic; Analysis; Alcoholic; Fatty

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）：长期大量饮酒是西方世界疾病和肝病死亡的主要原因。酒精性肝病（ALD）在临床和形态学上的特征很好，在疾病进展的三个主要阶段进行了描述：1）脂肪肝通常可抗抑制，2）酒精性肝炎或肝炎，以及3）cirrhosis或肝脏疤痕。需要新颖的治疗工具来治疗ALD。但是，要开发这种疗法，需要对有助于酒精诱发的肝损伤的每个阶段的分子机制进行彻底的了解。高通量技术的最新发展使差异表达基因产品的全球分析成为现实。我们建议制定一种定量蛋白质组学策略，以确定有助于ALD发展的分子机制。由于疾病进展的三个临床阶段中每个临床阶段的分子机制仍然鲜为人知，因此我们将重点介绍疾病生物发生：1）确定有助于ALD阶段1的分子机制，酒精脂肪肝病（AFLD），2）的分子机制，2） 通过与非酒精性脂肪肝疾病（NAFLD）的比较分析，以及3）随后选择/表征蛋白质生物标志物候选者，这些候选者可以区分酒精性和非酒精性脂肪肝肝脏，并导致建立标志性诊断板进行早期疾病进展。