Nuclear Receptor Function in Hepatic Pathology
Nuclear Receptor Function in Hepatic Pathology
批准号:
7350611
负责人:
DAVID D MOORE
金额:
$33.12万
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-08-01 至 2012-07-31
关键词:
AcetaminophenAreaCholestasisCirrhosisClassClinicalDiclofenacDiseaseFastingGenetic TranscriptionGenomicsHepaticHepatocyteHepatotoxicityHumanLiverMetabolicMetabolic DiseasesMicroRNAsMusNuclear ReceptorsPathologyPatientsPharmaceutical PreparationsPhaseRangeReactionReceptor ActivationRoleSamplingScreening procedureSignal TransductionStagingSystems BiologyTechnologyTestingTimebasedrug metabolismmouse modelnonalcoholic steatohepatitisreceptor expressionreceptor functionresponsetherapeutic targettroglitazonetype I and type II diabetes
中文摘要
与本项目特别相关的两个具体领域是筛选代谢信号的影响
和代谢疾病对肝脏microRNA表达的影响,以及NRs及其靶点在不良反应中的作用。
药物反应。该项目基于两个一般假设:1)微RNA表达改变,
反应核受体活化和其他代谢信号在肝脏中,允许非增殖性
肝细胞随着时间的推移改变其功能。2)药物不良反应中肝毒性的诱导是
与NR表达、其共调节因子和下游代谢产物的大规模改变相关。
靶点和不同类别的肝毒性剂引起不同的反应。我们将通过以下方式来检验这两种假设:
利用该链在最初开发的高通量QPCR筛选技术,
项目的第一阶段。
英文摘要
Two specific areas with particular relevance to this project arescreening for the impact of metabolic signals
and metabolic disease on hepatic expression of microRNAs, and the role of NRs and their targets in adverse
drug reactions. This project is based on two general hypotheses: 1) Micro RNA expression is altered in
response to nuclear receptor activation and other metabolic signals in the liver, allowing non-proliferative
hepatocytes to alter their function over time. 2) The induction of hepatotoxicity in adverse drug reactions is
associated with large scale alterations in expression of NRs, their coregulators and downstream metabolic
targets, and distinct classes of hepatotoxic agents elicit distinct responses. We will test both hypotheses by
leveraging the ongoing high throughput QPCR screening technologies developed by this Strand in the initial
Phase of the NURSA project.
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会议论文
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依托单位:
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