Physiological function of the novel Vitamin D receptor isoform

新型维生素 D 受体亚型的生理功能

• 批准号: nhmrc : 276414
• 负责人: Dr Luis Esteban
• 金额: $ 31.06万
• 依托单位: Garvan Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/physiological-function-novel-receptor-isoform/94555
• 关键词: Physiological; function; novel; Vitamin; receptor

Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form shows differences in activity from the shorter VDR form (VDRA) and also has an unusual distribution within the nucleus of the cell that may relate to its function. The present project focuses on further analysis of the relevance of this novel VDR isoform to normal physiology. We hypothesise that the larger VDR isoform has unique characteristics that may modify how vitamin D works in different cells and tissues, on specific target genes and in response to different active forms of vitamin D. These differences depend on this novel isoform s interaction with specific nuclear proteins that regulate the actions of other hormone receptors. The specific aims of this project are to study the functions of the novel VDR isoform in comparison to VDRA: * On different target genes that are either activated or inhibited in response to vitamin D, and on different cell lines from tissues where vitamin D has important roles, like intestine, kidney and bone * In their response to natural and synthetic vitamin D compounds, because of their possible therapeutic applications * In their interactions with intranuclear regulatory proteins, to understand the underlying mechanisms The study of these two forms of the VDR will help to clarify their potentially different cellular roles and their contribution to the wide range of physiological processes regulated by the vitamin D endocrine system. This understanding may open new paths for treatments of human bone and calcium-related diseases.

维生素D调节广泛的生理系统，包括那些涉及控制钙、血液水平和骨骼健康以及调节免疫系统和细胞生长的系统。维生素D的作用是通过维生素D受体(VDR)介导的，VDR是调节特定靶基因活性的蛋白质大家族中的一员，这些基因控制着许多生物功能。我们实验室最近描述了一种新颖的、更大形式的人类VDR。这种新颖的形式显示出与较短的VDR形式(VDRA)的活性差异，并且在细胞核内也有一种不寻常的分布，这可能与其功能有关。本项目的重点是进一步分析这种新的VDR亚型与正常生理学的相关性。我们推测，较大的VDR亚型具有独特的特征，可能会改变维生素D在不同细胞和组织中的作用方式，特定的靶基因，以及对不同活性形式的维生素D的反应。这些差异取决于这种新的异构体S与调节其他激素受体活动的特定核蛋白的相互作用。本项目的具体目的是研究新型VDR异构体与VDRA的功能比较：*在不同的靶基因上，对维生素D的反应被激活或抑制，以及在不同的细胞系上，维生素D在对天然和合成的维生素D化合物的反应中发挥重要作用*因为它们可能在治疗方面的应用*在它们与核内调节蛋白的相互作用中，了解潜在的机制这两种形式的VDR的研究将有助于阐明它们潜在的不同的细胞角色以及它们在维生素D内分泌系统调节的广泛生理过程中的贡献。这一认识可能为人类骨骼和钙相关疾病的治疗开辟新的途径。