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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 维甲酸（Retinoids），即全反式维甲酸（all-trans-retinoic acid，t-RA）和9-顺式维甲酸（9-cis-retinoic acid，9-cis-RA），是维生素A的衍生物，参与胚胎发生、细胞分化、增殖和免疫应答等多种生物学过程。 类维生素A通过充当两种核类维生素A受体的激动剂而发挥作用，这两种受体是配体依赖性异二聚体转录因子。 在类维生素A暴露后，核类维生素A受体增加或抑制类维生素A反应基因的基因表达，包括亚当斯（一种去整合素和金属蛋白酶）。 亚当斯是一种多结构域蛋白，被认为是一类新的整合素配体，并被充分表征为执行胞外域脱落的关键功能。 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-整联蛋白复合物的破坏。 通过遗传影响，类维生素A和相关代谢物通过改变亚当斯的丰度来控制脱落，从而直接影响ADAM-整联蛋白复合物的程度。 该提议建立了一个可测试的模型，该模型通过类维生素A受体的异二聚体伴侣的ADAM脱落将亚当斯和类维生素A直接与遗传调控偶联。