Role of Acetaldehyde on PDGF-BB-induced HSC Migration and Proliferation.
乙醛对 PDGF-BB 诱导的 HSC 迁移和增殖的作用。
基本信息
- 批准号:7228134
- 负责人:
- 金额:$ 31.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-04-01 至 2011-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcetaldehydeAlcoholsAreaBasement membraneCarpetCell AdhesionCell ProliferationCellsCicatrixCirrhosisCollagenCollagen GeneCollagen Type ICollagen Type IVDepositionDystroglycanEthanolEventExtracellular MatrixExtracellular Matrix ProteinsFibronectinsFibrosisGoalsGrowth FactorHepatic FibrogenesisHepatic Stellate CellHydrogen PeroxideImmigrationInjuryIntegrinsLaboratoriesLamininLaminin ReceptorLeadLiverLiver FibrosisMessenger RNAMolecularMyofibroblastPerisinusoidal SpacePlatelet-Derived Growth Factor ReceptorPlatelet-Derived Growth Factor beta ReceptorPlayPreventionProcessProductionProliferatingReactive Oxygen SpeciesRegulationReportingRoleSignal Transduction PathwayTestingTherapeutic InterventionTissuesTranscriptional ActivationUp-RegulationVentWorkbasecatalasecell motilityinterestmigrationplatelet-derived growth factor BBpreventreceptorreceptor expressionresponse
项目摘要
DESCRIPTION (provided by applicant): Liver injury is accompanied by trans-differentiation (activation) of hepatic stellate cells (HSC) into myofibroblasts, a key event in liver fibrogenesis that results in increased proliferation and migration. These vents are accompanied by alterations in the production of extracellular matrix components required for cell-matrix interactions and excess production of scar tissue, including type I collagen and fibronectin. Thus, inhibition of HSC trans-differentiation could prevent the subsequent events leading to excess collagen deposition, fibrosis and cirrhosis. A hallmark of HSC activation is the up-regulation of platelet-derived growth factor-beta receptor (PDGF-betaR) and their increased migratory and proliferative response to PDGF-BB. Although many studies have focused on PDGF-BB-dependent molecular events leading to cell proliferation and migration, little is known regarding the role of acetaldehyde, the first metabolite of ethanol, on PDGF-betaR expression and HSC proliferation and migration. Moreover, the role of ACH and PDGF-BB on HSC matrix interactions remains to be investigated. Based on our previous studies, namely that acetaldehyde exerts some of its action via the accumulation of reactive oxygen species (hydrogen peroxide) and the preliminary results presented in this application we propose to investigate molecular mechanisms whereby acetaldehyde modulates the expression of PDGF-betaR in HSC. We will also study the role of ACH on the migratory and proliferative responses of HSC to PDGF-BB and on the PDGF-BB-dependent alterations in cell-matrix interactions. Our long term goal is to unravel key molecular events triggered by acetaldehyde that could lead to therapeutic intervention and thus, to prevention and/or amelioration of alcohol-induced liver fibrosis and cirrhosis.
描述(由申请人提供):肝损伤伴随着肝星状细胞(HSC)向肌成纤维细胞的反分化(激活),这是肝纤维形成的关键事件,导致增殖和迁移增加。这些喷口伴随着细胞-基质相互作用所需的细胞外基质成分的产生改变和疤痕组织的过量产生,包括I型胶原蛋白和纤维连接蛋白。因此,抑制HSC的反式分化可以防止导致胶原沉积过多、纤维化和肝硬化的后续事件。HSC活化的一个标志是血小板衍生生长因子-受体(PDGF-betaR)的上调及其对PDGF-BB的迁移和增殖反应的增加。尽管许多研究都集中在导致细胞增殖和迁移的pdgf - bb依赖的分子事件上,但关于乙醇的第一代谢物乙醛在PDGF-betaR表达和HSC增殖和迁移中的作用知之甚少。此外,ACH和PDGF-BB在HSC基质相互作用中的作用仍有待研究。基于我们之前的研究,即乙醛通过活性氧(过氧化氢)的积累发挥其部分作用,以及本应用程序中提出的初步结果,我们建议研究乙醛调节HSC中PDGF-betaR表达的分子机制。我们还将研究ACH在HSC对PDGF-BB的迁移和增殖反应中的作用,以及在细胞-基质相互作用中PDGF-BB依赖性改变的作用。我们的长期目标是揭示由乙醛引发的关键分子事件,这些事件可能导致治疗干预,从而预防和/或改善酒精诱导的肝纤维化和肝硬化。
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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MARCOS ROJKIND其他文献
MARCOS ROJKIND的其他文献
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{{ truncateString('MARCOS ROJKIND', 18)}}的其他基金
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6371374 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6128654 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6629598 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
2389919 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6509228 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6495544 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6731971 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
2047189 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
Role of Acetaldehyde on PDGF-BB-induced HSC Migration
乙醛对 PDGF-BB 诱导的 HSC 迁移的作用
- 批准号:
7050518 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
7052752 - 财政年份:1995
- 资助金额:
$ 31.57万 - 项目类别:
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