Epigenetic regulation in liver fibrosis
肝纤维化的表观遗传调控
基本信息
- 批准号:10428589
- 负责人:
- 金额:$ 45.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAlcoholsAnimal ModelCCAAT-Enhancer-Binding ProteinsCaloriesCell DeathCell LineCell modelChromatinCirrhosisComplexCuesDataDeacetylaseDevelopmentDietDiseaseDisease ProgressionDrug toxicityEnvironmental Risk FactorEpigenetic ProcessExtracellular MatrixFamily memberFatty LiverFibrosisFoundationsFunctional disorderFutureGeneral PopulationGenesGeneticHepaticHepatic FibrogenesisHepatic Stellate CellHepatocyteHistone DeacetylaseHomologous ProteinHumanIn VitroInflammationInvestigationKnockout MiceKnowledgeLifeLinkLiverLiver FibrosisLiver diseasesLong-Term EffectsMissionMolecularMolecular ProfilingMusObesityPathogenesisPathway interactionsPatientsPhysiologicalPlayPrevalencePreventionPrimary carcinoma of the liver cellsProcessProductionProteinsPublic HealthRegulationResearchRoleSeveritiesSignal TransductionSirtuinsTestingTherapeutic InterventionTissuesTransgenic MiceUnited States National Institutes of HealthVirulence FactorsVirus Diseasesburden of illnesscell typechronic liver diseasechronic liver injurycommon treatmenteffective therapyendoplasmic reticulum stressepigenetic regulationepigenomicsexperimental studygenetic makeupglucose metabolismin vivolipid metabolismliver developmentliver injurymigrationmouse modelnew therapeutic targetnon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnovelsedentary lifestyletherapeutic developmenttherapeutically effectivetranscription factortranscriptomics
项目摘要
Project Summary
Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% adults in the US. NAFLD initially
manifests hepatic steatosis and progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and even cirrhosis
or hepatocellular carcinoma. Liver fibrosis, a condition of elevated accumulation of extracellular matrix in the
liver, is a strong indicator of NASH severity. In most NASH patients, environmental factors such as high-calorie
diets and sedentary lifestyle are primary contributors to the disease development. Those environmental cues
often modulate epigenetic and transcription factors to acquire long-term effects. In our preliminary study, we
have identified Sirtuin 6 (Sirt6) as a key suppressor of liver fibrosis. To further investigate the role of Sirt6 in the
pathogenesis of liver fibrosis, we plan to carry out both in vitro and in vivo experiments using cell and animal
models. Hepatic stellate cells are generally considered as a major contributor to the production of extracellular
matrix in the liver after chronic liver injury. Therefore, we will focus on the regulation of hepatic stellate cells by
Sirt6 at molecular, cellular, and tissue levels. It is expected that the proposed pathophysiological and
mechanistic investigation of liver fibrosis in this application will uncover key pathways or network that is
controlled by Sirt6. Moreover, the knowledge gained from this project can help develop therapeutic
interventions for hepatic fibrosis.
项目摘要
非酒精性脂肪肝(NAFLD)影响美国约30%的成年人。NAFLD最初
表现出肝脂肪变性并进展为非酒精性脂肪性肝炎(NASH)、纤维化甚至肝硬化
或肝细胞癌。肝纤维化是指肝细胞外基质在肝组织中积聚增加的一种情况。
肝脏是NASH严重程度的强指标。在大多数NASH患者中,环境因素如高热量
饮食和久坐不动的生活方式是导致疾病发展的主要因素。那些环境线索
通常调节表观遗传和转录因子以获得长期效应。在初步研究中,我们
已经鉴定Sirtuin 6(Sirt6)为肝纤维化的关键抑制因子。为了进一步研究Sirt6在
肝纤维化的发病机制,我们计划使用细胞和动物进行体外和体内实验,
模型肝星状细胞通常被认为是产生细胞外基质的主要贡献者。
慢性肝损伤后肝内基质的变化。因此,我们将重点关注肝星状细胞的调节,
Sirt6在分子、细胞和组织水平上的表达。预期所提出的病理生理学和
在该应用中,肝纤维化的机制研究将揭示肝纤维化的关键途径或网络,
由Sirt6控制此外,从这个项目中获得的知识可以帮助开发治疗
肝纤维化的治疗
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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{{ truncateString('X Charlie Dong', 18)}}的其他基金
The pathophysiological function of PNPLA3-148M variant in alcohol-induced liver injury
PNPLA3-148M变异在酒精性肝损伤中的病理生理作用
- 批准号:
10366395 - 财政年份:2022
- 资助金额:
$ 45.71万 - 项目类别:
Role of SIRT6 in the pancreatic beta cell aging
SIRT6在胰腺β细胞衰老中的作用
- 批准号:
10371337 - 财政年份:2022
- 资助金额:
$ 45.71万 - 项目类别:
Role of SIRT6 in the pancreatic beta cell aging
SIRT6在胰腺β细胞衰老中的作用
- 批准号:
10641670 - 财政年份:2022
- 资助金额:
$ 45.71万 - 项目类别:
The pathophysiological function of PNPLA3-148M variant in alcohol-induced liver injury
PNPLA3-148M变异在酒精性肝损伤中的病理生理作用
- 批准号:
10613405 - 财政年份:2022
- 资助金额:
$ 45.71万 - 项目类别:
Role of ATG14 in the regulation of hepatic function
ATG14在肝功能调节中的作用
- 批准号:
10596539 - 财政年份:2020
- 资助金额:
$ 45.71万 - 项目类别:
Role of ATG14 in the regulation of hepatic function
ATG14在肝功能调节中的作用
- 批准号:
10371047 - 财政年份:2020
- 资助金额:
$ 45.71万 - 项目类别:
Role of sirtuin 6 in the protection of liver from the alcohol-induced injury
Sirtuin 6在保护肝脏免受酒精损伤中的作用
- 批准号:
9244917 - 财政年份:2017
- 资助金额:
$ 45.71万 - 项目类别:
Sestrin3 in the pathogenesis of alcoholic and non-alcoholic fatty liver disease
Sestrin3 在酒精性和非酒精性脂肪肝发病机制中的作用
- 批准号:
9303199 - 财政年份:2016
- 资助金额:
$ 45.71万 - 项目类别:
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