Nuclear receptor regulation of bile acid metabolism

核受体调节胆汁酸代谢

• 批准号: 9108991
• 负责人: Sayeepriyadarshini Anakk
• 金额: $ 7.41万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-10 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9108991
• 关键词: Adolescent; Adult; Age; Back; Bile Acid Biosynthesis Pathway; Bile Acids; Bile fluid; Biliary; Biological; Birth; Cholestasis; Complex; Cues; Defect; Detergents; Development; Diagnosis; Dietary Fats; Disease; Enterohepatic Circulation; Fatty acid glycerol esters; Gallbladder; Gene Targeting; Genes; Genetic; Goals; Health; Hepatic; Homeostasis; Hormonal; Incidence; Individual; Infant; Intervention; Intestines; Knockout Mice; Lead; Liver; Liver diseases; Mediating; Metabolism; Microarray Analysis; Molecular; Molecular Profiling; Multi-Drug Resistance; Mus; Neonatal; Nuclear Receptors; Pathway interactions; Physiological; Pump; Receptor Signaling; Regulation; Research; Role; Signal Pathway; Small Intestines; Staging; Symptoms; Therapeutic; Tissues; bile salts; cytotoxic; early onset; feeding; insight; liver transplantation; mouse model; novel; novel diagnostics; novel therapeutics; receptor; response; tool

 DESCRIPTION (provided by applicant): Cholestasis, retention of bile acids in the liver, is a leading cause for liver transplantation. Excess amounts of bile acids are cytotoxic and are therefore tightly regulated by nuclear receptors Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP). Bile acids are synthesized in the liver and secreted into the intestine for digesting dietary fat. This proposal aims to determine coordinate role of FXR and SHP in controlling bile acid levels in liver and in intestine using genetic mouse models. Successful completion of this project would result in identification of FXR and SHP driven transcriptional gene networks in these above-mentioned tissues. These pilot results will enable us to perform detailed analysis and provide mechanistic insights into the underpinnings of cholestasis.

 描述（由申请人提供）：胆汁淤积（胆汁酸在肝脏中的滞留）是肝移植的主要原因，过量的胆汁酸具有细胞毒性，因此受到核受体法尼醇 X 受体 (FXR) 和小异二聚体伴侣的严格调节。 (SHP)。胆汁酸在肝脏中合成并分泌到肠道中用于消化膳食脂肪。该提案旨在确定 FXR 和 SHP 在控制中的协调作用。使用遗传小鼠模型检测肝脏和肠道中的胆汁酸水平将导致在上述组织中鉴定 FXR 和 SHP 驱动的转录基因网络。这些试点结果将使我们能够进行详细分析并提供机制。深入了解胆汁淤积的基础。