EFFECT OF RETINOID METABOLISM ON ADAM-INTEGRIN INTERACTIONS IN HUMAN BLOOD CELL

维生素A代谢对人血细胞中ADAM-整合素相互作用的影响

• 批准号: 8168104
• 负责人: Melissa Hernandez
• 金额: $ 1.98万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-19 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168104
• 关键词: Agonist; Biological Process; Blood Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Couples; Disease; Disintegrins; Embryonic Development; Event; Funding; Gene Expression; Genes; Genetic; Grant; Human; Immune response; Institution; Integrins; Ligands; Mediating; Metabolism; Metalloproteases; Modeling; Nuclear; Proteins; Regulation; Research; Research Personnel; Resources; Retinoid Receptor; Retinoids; Source; Tretinoin; United States National Institutes of Health; Vitamin A; alitretinoin; data modeling; novel; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Retinoids, all-trans-retinoic acid (t-RA) and 9-cis-retinoic acid (9-cis-RA), are vitamin A derivatives that mediate a variety of integral biological processes including embryogenesis, cellular differentiation, proliferation, and immune response. Retinoids elicit their effects by acting as agonists for two nuclear retinoid receptors that are ligand dependent heterodimeric transcription factors. Upon retinoid exposure, nuclear retinoid receptors augment or dampen gene expression of retinoid responsive genes, including ADAMS (a disintegrin and metalloprotease). ADAMs are multidomain proteins that are recognized as a novel class of integrin ligand and are well characterized for executing the critical function of ectodomain shedding. Current models and data attribute abnormal shedding events associated with disease states to aberrant ADAM expression levels and/or disruption of ADAM-integrin complexes. Through genetic influence, retinoids and relevant metabolites plausibly govern shedding by altering the abundance of ADAMs and thereby directly impact the extent of ADAM-integrin complexes. This proposal establishes a testable model that couples ADAMs and retinoids directly to genetic regulation through ADAM shedding of a heterodimeric partner of a retinoid receptor.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 类维生素A、全反式视黄酸 (t-RA) 和 9-顺式视黄酸 (9-cis-RA) 是维生素 A 衍生物，可介导多种完整的生物过程，包括胚胎发生、细胞分化、增殖和免疫回复。 类维生素A通过作为两种核类维生素A受体的激动剂来发挥其作用，这两种核类维生素A受体是配体依赖性异二聚体转录因子。 暴露于类维生素A后，核类维生素A受体会增强或抑制类维生素A反应基因的基因表达，包括ADAMS（解整合素和金属蛋白酶）。 ADAM 是多域蛋白，被认为是一类新型整联蛋白配体，并且具有执行胞外域脱落的关键功能的良好特征。 目前的模型和数据将与疾病状态相关的异常脱落事件归因于异常的 ADAM 表达水平和/或 ADAM 整合素复合物的破坏。 通过遗传影响，类维生素A和相关代谢物可能通过改变ADAM的丰度来控制脱落，从而直接影响ADAM-整合素复合物的程度。 该提案建立了一个可测试的模型，通过 ADAM 脱落类视黄醇受体的异二聚体伙伴，将 ADAM 和类视黄醇直接耦合到基因调控。