Tumor Necrosis Superfamily Ligands and Lymphocytes Role in Liver Regeneration

肿瘤坏死超家族配体和淋巴细胞在肝脏再生中的作用

基本信息

批准号：
8217231
负责人：
ROBERT A. ANDERS
金额：
$ 33.24万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-05 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8217231
关键词：
Abbreviations Address Alanine Transaminase American Antibodies Apoptosis Biological Assay Bone Marrow Bromodeoxyuridine Cause of Death Cell Death Cell Survival Cells Cessation of life Chimeric Proteins Complex Culture Media Cyclin D1 Cyclin E DNA biosynthesis Data Disease Event Exhibits Family member Fibroblasts Genetic Glycoproteins Goals Hepatic Hepatitis Hepatocyte Herpesviridae Hour IL6 gene Immune In Vitro Injury Interleukin-6 Intravenous Kinetics Knock-out Laboratories Lead Ligands Light Link Lipopolysaccharides Liver Liver Regeneration Liver diseases Lymphocyte MAP Kinase Gene Malignant neoplasm of liver Mediating Mediator of activation protein Medical Membrane Modeling Molecular Monitor Mus N-terminal NF-kappa B Natural regeneration Necrosis Partial Hepatectomy Pathway interactions Phosphorylation Phosphotransferases Population Production Proteins Resistance Reverse Transcriptase Polymerase Chain Reaction Role STAT3 gene Serum Signal Pathway Signal Transduction Small Interfering RNA Source System T-Lymphocyte Testing Therapeutic Time Tissues Tumor Necrosis Factor-Beta Tumor Necrosis Factor-alpha United States Viral Viral hepatitis cell type chronic liver disease cytokine extracellular feeding high voltage electron microscopy improved in vitro testing in vivo Model intrahepatic lymphotoxin beta lymphotoxin beta receptor member mortality prevent programs public health relevance receptor regenerative response stress-activated protein kinase 1 trafficking tumor

项目摘要

DESCRIPTION (provided by applicant): A remarkable feature of the vertebrate liver is its ability to regenerate following injury. Multiple parallel pathways feed into the regenerative response. We believe that unlocking the systems that control the regenerative response will lead to treatments for liver diseases. We are focusing upon the tumor necrosis factor (TNF) superfamily which is a large group of ligands and receptors with diverse biologic activities. Our laboratory is uncovering the exact intra- and extrahepatocellular events of the TNF related member, lymphotoxin. Specifically, we are examining the mechanisms by which this potent molecule contributes to liver regeneration. We are focusing upon the interactions between the lymphotoxin receptor on hepatocytes and lymphotoxin expressed on immune cells. First, we aim to show what cell survival mechanisms the lymphotoxin beta receptor triggers. Second, we link the production of interleukin 6 and stimulation of STAT3 phosphorylation to the lymphotoxin receptor. Third, we specifically tie the lymphotoxin receptor to the production of IL-6 and the intrahepatic cellular response. Together these aims will define the role of TNF superfamily member in liver regeneration and lead to a better understanding of what causes and could potentially prevent liver injury. PUBLIC HEALTH RELEVANCE: Liver diseases are among the leading causes of death for Americans and few treatments options exist. Our laboratory seeks to understand how the liver responds to injuries. What we discover is relevant to livers diseases such as viral and non-viral hepatitis, chronic liver disease and liver cancer.

描述（由申请人提供）：脊椎动物肝脏的显着特征是其受伤后再生能力。多个平行途径馈入再生反应。我们认为，解锁控制再生反应的系统将导致肝病的治疗。我们关注的是肿瘤坏死因子（TNF）超家族，这是一大批具有不同生物学活性的配体和受体。我们的实验室正在揭示与TNF相关成员淋巴毒素的确切和外eP骨外事件。具体而言，我们正在研究该有效分子有助于肝脏再生的机制。我们关注淋巴毒素受体在肝细胞上的相互作用和在免疫细胞上表达的淋巴毒素之间的相互作用。首先，我们旨在展示哪些细胞存活机制淋巴毒素β受体触发器。其次，我们将白介素6的产生和STAT3磷酸化的刺激与淋巴毒素受体联系起来。第三，我们将淋巴细胞毒素受体专门将IL-6的产生和肝内细胞反应绑定。这些目标共同定义了TNF超家族在肝脏再生中的作用，并可以更好地理解原因，并可能预防肝损伤。公共卫生相关性：肝病是美国人的主要死亡原因之一，几乎没有治疗选择。我们的实验室试图了解肝脏如何应对伤害。我们发现的与肝病有关，例如病毒和非病毒肝炎，慢性肝病和肝癌。