R-spondin1-LGR4 Signaling and Ischemia/Reperfusion Injury in Steatotic Liver
脂肪肝中的 R-spondin1-LGR4 信号转导和缺血/再灌注损伤
基本信息
- 批准号:9303031
- 负责人:
- 金额:$ 40.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-01 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAmericanAreaBiologicalCellsComplexCouplesDataDevelopmentDisciplineEnergy SupplyFRAP1 geneFatty LiverG-Protein-Coupled ReceptorsG-substrateGTP-Binding ProteinsHealthHepaticHepatic TissueHepatocyteInjuryInjury to LiverLeucine-Rich RepeatLigandsLipidsLiverMedicalMolecularMorbidity - disease rateNamesNutrientPathway interactionsPatientsPhysiologicalPhysiologyPredispositionPreventionPrevention strategyProtein FamilyReperfusion InjurySignal PathwaySignal TransductionSocietiesStressSystemTechniquesTimeTransgenic Organismsbeta cateninhypoxia inducible factor 1insightliver injurymembermortalitynon-alcoholic fatty livernovelreceptorsensortreatment strategy
项目摘要
Project Summary
Non-alcoholic fatty liver disease represents a group of conditions associated with excessive lipid accumulation
in hepatocytes. Hepatic steatosis affects almost 30% of adults and imposes a major health burden on
American society. Non-alcoholic fatty liver disease increases morbidity and mortality associated with injury or
physiological stress, and thus is a concern for all medical disciplines. Our preliminary studies have identified a
novel molecular pathway and novel cellular mechanisms that couple long-term energy supply to steatosis and
injury.
Our studies demonstrate for the first time that a member of the leucine-rich repeat-containing G protein-
coupled receptors, LGR4, is expressed in hepatocytes. R-spondin family proteins were recently identified as
ligands for LGR4. Our preliminary data also indicate that R-spondin1 is produced by hepatocytes and that R-
spondin1-LGR4 signaling is present in the liver. Distinct from classical G protein-coupled receptors which act
via G proteins, hepatic LGR4 functions mainly through Wnt/β-catenin signaling.
Further, preliminary studies indicate that the mechanistic target of rapamycin complex 1 (mTORC1) in liver
couples long-term nutrient status to R-spondin1-LGR4 expression. Steatosis down regulates hepatic R-
spondin1/LGR4 and renders hepatic tissue more vulnerable to injury. We propose to investigate the function
of the hepatic R-spondin1-LGR4 system using cell biological and transgenic techniques. Completion of this
proposal will advance a completely new area of hepatic physiology and will provide novel insights into to liver
injury.
项目摘要
非酒精性脂肪性肝病代表了一组与脂质过度积聚相关的疾病
在肝细胞中。肝脏脂肪变性影响近30%的成年人,并对他们造成重大的健康负担。
美国社会非酒精性脂肪肝增加了与损伤或
生理压力,因此是所有医学学科关注的问题。我们的初步研究发现
新的分子途径和新的细胞机制,将长期能量供应与脂肪变性相结合,
损伤
我们的研究首次证明了富含亮氨酸重复序列的G蛋白的一个成员-
偶联受体LGR 4在肝细胞中表达。R-spondin家族蛋白最近被鉴定为
LGR 4的配体。我们的初步数据还表明,R-spondin 1是由肝细胞产生的,而R-spondin 1是由肝细胞产生的。
Spondin 1-LGR 4信号传导存在于肝脏中。与经典的G蛋白偶联受体不同,
肝脏LGR 4主要通过Wnt/β-catenin信号通路发挥作用。
此外,初步研究表明,雷帕霉素复合物1(mTORC 1)在肝脏中的机制靶点
将长期营养状态与R-spondin 1-LGR 4表达相结合。脂肪变性下调肝脏R-
spondin 1/LGR 4并使肝组织更容易受到损伤。我们建议研究函数
的肝R-spondin 1-LGR 4系统使用细胞生物学和转基因技术。完成本
该提案将推进肝脏生理学的一个全新领域,并将为肝脏提供新的见解
损伤
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MICHAEL W. MULHOLLAND其他文献
MICHAEL W. MULHOLLAND的其他文献
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{{ truncateString('MICHAEL W. MULHOLLAND', 18)}}的其他基金
Gastric X/A Like Cells in Health and Diseases
健康和疾病中的胃 X/A 样细胞
- 批准号:
10183235 - 财政年份:2018
- 资助金额:
$ 40.87万 - 项目类别:
Gastric X/A Like Cells in Health and Diseases
健康和疾病中的胃 X/A 样细胞
- 批准号:
9438610 - 财政年份:2018
- 资助金额:
$ 40.87万 - 项目类别:
Gastric X/A Like Cells in Health and Diseases
健康和疾病中的胃 X/A 样细胞
- 批准号:
10399643 - 财政年份:2018
- 资助金额:
$ 40.87万 - 项目类别:
R-spondin1-LGR4 Signaling and Ischemia/Reperfusion Injury in Steatotic Liver
脂肪肝中的 R-spondin1-LGR4 信号转导和缺血/再灌注损伤
- 批准号:
9896813 - 财政年份:2017
- 资助金额:
$ 40.87万 - 项目类别:
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