The Role of Glucocorticoids in Cell Fate Determination
糖皮质激素在细胞命运决定中的作用
基本信息
- 批准号:7252424
- 负责人:
- 金额:$ 13.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-01 至 2011-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdipocytesAdipose tissueAdverse effectsAsthmaAutoimmune DiseasesBiological AssayCell Differentiation processCell Fate ControlCellsCentral obesityConditionDevelopmentDiabetes MellitusDiseaseDyslipidemiasFetusGene TargetingGenesGlucocorticoidsGoalsGraft RejectionHealth SciencesHypertensionInsulin ResistanceKnockout MiceLeadLightMalignant NeoplasmsMedicalMesenchymalMetabolic syndromeMolecularMolecular Biology TechniquesMusNeuroblastomaObesityOsteoblastsOsteoporosisPathogenesisPathway interactionsPatientsPhenotypePhysiologyPlayProcessRangeRegulationResearchResearch PersonnelRheumatoid ArthritisRoleSigns and SymptomsStructure of parenchyma of lungTransgenic MiceTransgenic Organismsadipocyte differentiationbasecell typein vivoinsightinsulin sensitivityleukemialipid biosynthesismouse modelmyostatinpremature lungsprogramsreceptor
项目摘要
DESCRIPTION (provided by applicant):
The goal of this research is to investigate how glucocorticoids (GCs) regulate the differentiation of pluripotent cells into adipocytes and the role of myostatin, a GC regulated gene, in directing this process. The long term objectives are to understand how GCs, acting via their receptor (GR), influence cell fate determination and differentiation. GCs have been used to therapeutically induce differentiation of a broad range of cell types including premature lung tissue in the fetus and immature malignancies such as leukemia and neuroblastoma. GCs have also been used as therapy for a wide range of medical conditions including transplant rejection, asthma, rheumatoid arthritis and other autoimmune diseases. Interestingly, the side effects of GC excess have a signifcant overlap with the signs and symptoms of insulin resistance and the metabolic syndrome. However, a direct connection between GC activity and the development of the metabolic syndrome has yet to be elucidated. The aim of this study study is to examine the hypothesis that the same pathways involved in GC regulation of cell fate determination and differentiation programs may contribute to the development of some of the side effects found in patients with GC excess such as obesity and insulin resistance. The overall goal is to understand how GCs regulate cell fate and the role this pathway plays in both physiology and disease. This project will focus on the regulation of a GC target gene (myostatin) and the implications of this regulation on: cell fate determination, adipogenesis and insulin sensitivity. There are three specific aims: (1) to investigate the regulation of myostatin by GCs in pluripotent mesenchymal cells in order to assess the effect on cell fate determination, (2) to analyze of the role of GR and myostatin in adipogenesis in vivo, and (3) to evaluate the role of GR in adipocyte differentiation and in the pathophysiological changes in GC related diseases and determine if myostatin is relevant to GR's role in these diseases. This project will use molecular biology techniques and genetically modified mouse models, including transgenics and knock-outs, to elucidate the mechanisms by which GCs regulate myostatin with a focus on adipocyte cell fate. This research will provide insight into the cause of the debilitating side effects of GC therapy that millions of people suffer from. In addition, it will shed light on the mechanisms of GC action which has important implications for understanding the development of diseases such as diabetes.
描述(由申请人提供):
本研究的目的是研究糖皮质激素(GC)如何调节多能细胞向脂肪细胞的分化,以及肌生长抑制素(GC 调节基因)在指导这一过程中的作用。长期目标是了解 GC 如何通过其受体 (GR) 发挥作用,影响细胞命运决定和分化。 GC已被用于治疗性诱导多种细胞类型的分化,包括胎儿的早产肺组织和白血病和神经母细胞瘤等未成熟的恶性肿瘤。 GC 还被广泛用于治疗多种疾病,包括移植排斥、哮喘、类风湿性关节炎和其他自身免疫性疾病。有趣的是,GC 过量的副作用与胰岛素抵抗和代谢综合征的体征和症状有明显的重叠。然而,GC 活性与代谢综合征发生之间的直接联系尚未阐明。本研究的目的是检验以下假设:参与 GC 调节细胞命运决定和分化程序的相同途径可能导致 GC 过量患者中发现的一些副作用(如肥胖和胰岛素抵抗)的发生。总体目标是了解 GC 如何调节细胞命运以及该途径在生理学和疾病中发挥的作用。该项目将重点关注 GC 靶基因(肌生长抑制素)的调节以及该调节对以下方面的影响:细胞命运决定、脂肪生成和胰岛素敏感性。有三个具体目标:(1)研究多能间充质细胞中GC对肌肉生长抑制素的调节,以评估其对细胞命运决定的影响,(2)分析GR和肌肉生长抑制素在体内脂肪生成中的作用,以及(3)评价GR在脂肪细胞分化和GC相关疾病的病理生理变化中的作用,并确定肌生长抑制素是否与GR在这些疾病中的作用相关。该项目将利用分子生物学技术和转基因小鼠模型(包括转基因和基因敲除)来阐明 GC 调节肌肉生长抑制素的机制,重点关注脂肪细胞的命运。这项研究将深入了解 GC 疗法导致数百万人遭受的令人衰弱的副作用的原因。此外,它将揭示 GC 的作用机制,这对于了解糖尿病等疾病的发展具有重要意义。
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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Brian J Feldman其他文献
Brian J Feldman的其他文献
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{{ truncateString('Brian J Feldman', 18)}}的其他基金
Molecular responses and physiological implications to systemic stimuli in adipocyte progenitor cells
脂肪祖细胞对全身刺激的分子反应和生理学意义
- 批准号:
10420760 - 财政年份:2022
- 资助金额:
$ 13.08万 - 项目类别:
Molecular responses and physiological implications to systemic stimuli in adipocyte progenitor cells
脂肪祖细胞对全身刺激的分子反应和生理学意义
- 批准号:
10615751 - 财政年份:2022
- 资助金额:
$ 13.08万 - 项目类别:
Integrated Systemic and Adipose Depot-Specific Regulation of Adipogenesis
脂肪生成的综合系统和脂肪库特异性调节
- 批准号:
10163160 - 财政年份:2019
- 资助金额:
$ 13.08万 - 项目类别:
Using Components of the Circadian Clock to Regulate Stem Cell Fate Decisions
利用生物钟的组成部分来调节干细胞的命运决定
- 批准号:
7942482 - 财政年份:2010
- 资助金额:
$ 13.08万 - 项目类别:
The Role of Glucocorticoids in Cell Fate Determination
糖皮质激素在细胞命运决定中的作用
- 批准号:
7643239 - 财政年份:2006
- 资助金额:
$ 13.08万 - 项目类别:
The Role of Glucocorticoids in Cell Fate Determination
糖皮质激素在细胞命运决定中的作用
- 批准号:
7429813 - 财政年份:2006
- 资助金额:
$ 13.08万 - 项目类别:
The Role of Glucocorticoids in Cell Fate Determination
糖皮质激素在细胞命运决定中的作用
- 批准号:
7141363 - 财政年份:2006
- 资助金额:
$ 13.08万 - 项目类别:
The Role of Glucocorticoids in Cell Fate Determination
糖皮质激素在细胞命运决定中的作用
- 批准号:
7892581 - 财政年份:2006
- 资助金额:
$ 13.08万 - 项目类别:
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