权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of Bile Acids in the Initiation of Liver Regeneration

胆汁酸在肝脏再生启动中的作用

基本信息

批准号：
8608520
负责人：
Willscott E Naugler
金额：
$ 14.85万
依托单位：
OREGON HEALTH & SCIENCE 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：
2010-03-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8608520
关键词：
Acute Liver Failure Artificial Liver Back Bile Acids Bile fluid Biliary Bilirubin Blood Blood Coagulation Disorders Cell division Cells Cholestasis Cholesterol Cirrhosis Clinical Comprehension Data Dependovirus Detergents Development Disease Distal part of ileum Down-Regulation Encephalopathies Environment Equipment Event Excision Excretory function Fatty acid glycerol esters Fellowship Five-Year Plans Funding Gastroenterology Gene Expression Regulation Genetic Genetic Programming Goals Health Health Sciences Hepatic Hepatic Mass Hepatocarcinogenesis Hepatocyte Hepatology Hepatotoxicity Homeostasis Human Resources In Vitro Inflammation Injury Injury to Liver Internal Medicine Intestines Knowledge Laboratories Ligands Lipids Liver Liver Regeneration Liver Stem Cell Liver diseases Malignant neoplasm of liver Mediating Mediator of activation protein Membrane Transport Proteins Mentors Methods Modeling Molecular Biology Morbidity - disease rate Mus National Institute of Diabetes and Digestive and Kidney Diseases Natural regeneration Nuclear Receptors Operative Surgical Procedures Oregon Outcome Outcome Study Partial Hepatectomy Pathway interactions Perfusion Pharmaceutical Preparations Physiological Physiology Portal vein structure Postdoctoral Fellow Prevention Process Receptor Signaling Recovery Research Research Personnel Residencies Rodent Rodent Model Role Serum Signal Transduction System Testing Toxic effect Translational Research Transplantation Universities Work absorption base bile salts biliary tract blood glucose regulation career in vivo in vivo Model innovation liver cell proliferation liver function liver injury mortality prevent programs receptor regenerative response small hairpin RNA solute uptake

项目摘要

DESCRIPTION (provided by applicant): This research focuses on liver regeneration and the initial triggers of this phenomenon. Bile acids are detergent molecules made from cholesterol which help solubilize fats for absorption in the intestine. Bile acids are made by hepatocytes, excreted into the intestine, and recirculated with little loss each day. The hypothesis of this proposal is that when the uninjured non-cholestatic liver encounters bile acids exceeding the maximum secretory capacity of the liver, regeneration is initiated. Aim 1 will determine the role of bile acids in the initiation of liver regeneration using a model of partial hepatectomy. In Aim 2 a model of bile acid administration through the portal vein will allow the focused study of the effects of supraphysiolgic levels bile acids on the liver in the absence of other injury. Lastly, Aim 3 will examine the contribution of the bile acid influx transporter and nuclear receptor signaling in bile acid-dependent liver regeneration. In summary, these studies will closely examine the effects of bile acids on the unobstructed liver, and determine how bile acids are involved in the triggering of liver regeneration. This proposal describes a five year plan for the development of an academic career in translational research in the field of Hepatology. The prinicipal [sic] investigator has completed a residency in Internal Medicine, a fellowship in Gastroenterology, and a post-doctoral fellowship in a laboratory focused on gene regulation and signal transduction in the context of hepatic inflammation. The proposal will promote the primary investigator's command of molecular biology and physiology as it relates liver regeneration and hepatocarcinogenesis, and prepare him for a career as an independent investigator. Dr. Markus Grompe will mentor the scientific aspects of the proposal, and the primary investigator has assembled a team of advisors who will assist in achieving the scientific and career goals outlined in the proposal. Dr. Grompe is a recognized leader in the field hepatocyte proliferation and is well-equipped to mentor this project. The laboratory is well-funded, has the appropriate equipment and support personnel, and exists in an environment supportive of this type of research at Oregon Health & Sciences University. PUBLIC HEALTH RELEVANCE: This contribution is significant because it is expected to provide a physiological reason for liver regeneration which can be used to manipulate hepatocyte proliferation for the purposes of preventing and treating the most common liver disease states.

描述（由申请人提供）：这项研究的重点是肝再生和这种现象的最初触发因素。胆汁酸是由胆固醇制成的清洁剂分子，有助于溶解脂肪以便在肠道中吸收。胆汁酸由肝细胞产生，排泄到肠道中，每天再循环，损失很少。该提议的假设是，当未受伤的非胆汁淤积性肝脏遇到超过肝脏最大分泌能力的胆汁酸时，就会启动再生。目标 1 将使用部分肝切除模型确定胆汁酸在肝再生启动中的作用。在目标 2 中，通过门静脉施用胆汁酸的模型将允许重点研究在没有其他损伤的情况下超生理水平胆汁酸对肝脏的影响。最后，目标 3 将检查胆汁酸流入转运蛋白和核受体信号传导在胆汁酸依赖性肝脏再生中的贡献。总之，这些研究将仔细检查胆汁酸对畅通肝脏的影响，并确定胆汁酸如何参与触发肝脏再生。该提案描述了肝病学领域转化研究学术生涯发展的五年计划。首席研究员已完成内科住院医师实习、胃肠病学研究员以及实验室的博士后研究员，重点研究肝脏炎症背景下的基因调控和信号转导。该提案将促进主要研究者对与肝再生和肝癌发生相关的分子生物学和生理学的掌握，并为他作为独立研究者的职业生涯做好准备。马库斯·格罗姆普 (Markus Grompe) 博士将指导该提案的科学方面，主要研究者已组建了一个顾问团队，他们将协助实现提案中概述的科学和职业目标。 Grompe 博士是肝细胞增殖领域公认的领导者，完全有能力指导该项目。该实验室资金充足，拥有适当的设备和支持人员，并且存在于俄勒冈健康与科学大学支持此类研究的环境中。公共卫生相关性：这一贡献意义重大，因为它有望为肝再生提供生理学原因，可用于操纵肝细胞增殖，以达到预防和治疗最常见肝病状态的目的。