The Role of Hippo Pathway in Liver Regeneration

Hippo 通路在肝脏再生中的作用

• 批准号: 8096700
• 负责人: ROBERT A. ANDERS
• 金额: $ 34.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-10 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8096700
• 关键词: Abbreviations; Acute; Acute Hepatitis; Address; Alanine Transaminase; Apolipoprotein E; Apoptosis; Bromodeoxyuridine; CMV promoter; Cause of Death; Cell Cycle; Cell Death; Cell division; Cessation of life; Chronic; Chronic Hepatitis; Cirrhosis; Complementary DNA; Cyclin-Dependent Kinases; Cyclins; DNA biosynthesis; Data; Defect; Deoxyuridine; Development; Disease; Engineering; Gene Expression; Genes; Goals; Growth; Health; Hepatocarcinogenesis; Hepatocyte; Hepatocyte Growth Factor; Hepatomegaly; Knockout Mice; Lead; Link; Liver; Liver Regeneration; Liver diseases; Mediating; Modeling; Morbidity - disease rate; Mus; NOS2A gene; Nitric Oxide; Partial Hepatectomy; Pathway interactions; Physiological Processes; Positioning Attribute; Process; Production; Proliferating Cell Nuclear Antigen; Proteins; Proto-Oncogene Protein c-met; Resistance; Response Elements; Role; Signal Transduction; Tetracyclines; Transgenic Mice; Tumor Suppressor Proteins; United States; burden of illness; improved; in vivo; in vivo Model; inhibitor/antagonist; liver cell proliferation; liver transplantation; meetings; new therapeutic target; novel; prevent; pro-hepatocyte growth factor; promoter; regenerative

DESCRIPTION (provided by applicant): Liver diseases are among the 10 leading causes of death in the United States. The liver's extraordinary regenerative capacity is critical to understanding the mechanisms leading to developmental defects, acute and chronic liver diseases, and liver carcinogenesis. Stimulation of hepatocyte proliferation while preventing apoptosis is essential to the liver's regenerative process. Recently we uncovered a tumor suppressor pathway has potent effects upon liver cell division and death. Our long range goal is to define the cellular mechanisms underlying liver regeneration in health and disease and to apply these findings to developing improved therapies for liver disease. To that end, we are uniquely capable to address the objectives of this application, which are to uncover the mechanism that leads to the novel tumor suppressors' profound effects upon the liver. The central hypothesis of this proposal is that: The tumor suppressor controls liver celgrowth factor pathway in controlling liver size. At the end of the study we will better understand the growth and death of liver cells. This will help develop treatment for many liver diseases such as liver transplantation, cirrhosis, acute and chronic hepatitis.

描述(申请人提供)：肝病是美国十大主要死因之一。肝脏非凡的再生能力对于理解导致发育缺陷、急性和慢性肝病以及肝癌发生的机制至关重要。促进肝细胞增殖的同时防止细胞凋亡对肝脏的再生过程是必不可少的。最近，我们发现一种肿瘤抑制通路对肝细胞分裂和死亡有很强的作用。我们的长期目标是确定健康和疾病中肝脏再生的细胞机制，并将这些发现应用于开发改进的肝病治疗方法。为此，我们独一无二地有能力解决这一应用的目标，即揭示导致新型肿瘤抑制物对肝脏产生深刻影响的机制。这一建议的中心假设是：在控制肝脏大小的过程中，肿瘤抑制因子控制着肝细胞生长因子途径。在研究结束时，我们将更好地了解肝细胞的生长和死亡。这将有助于开发许多肝病的治疗方法，如肝移植、肝硬变、急性和慢性肝炎。