Deciphering the protective effect of the transient marker gene, Dhcr24, in the adrenal gland inner cortex.

解读肾上腺内皮质中瞬时标记基因 Dhcr24 的保护作用。

• 批准号: 10581620
• 负责人: Chen-Che Jeff Huang
• 金额: $ 7.47万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10581620
• 关键词: Adrenal Cortex; Adrenal Glands; Affect; Age; Aging; Alzheimer' s Disease; Amphibia; Amyloid; Apoptosis; Apoptotic; Biological Metamorphosis; Brain region; Cell Aging; Cell Differentiation process; Cell Proliferation; Cell Survival; Cells; Data; Development; Developmental Process; Excision; Failure; Feasibility Studies; Genes; Genetic Transcription; Goals; Grant; Hand; Histologic; Hormone Responsive; Human; Knockout Mice; Mammals; Mediating; Mediator; Modeling; Mus; Neurons; Organism; Oxidative Stress; Pathway interactions; Phenotype; Pilot Projects; Prevention; Retina; Role; Techniques; Testing; Thinness; Thyroid Gland; Thyroid Hormones; Tissues; Up-Regulation; adrenal cortex tumor; age related; aged; capsule; cell age; cell cortex; conditional knockout; differential expression; hormonal signals; mouse model; next generation sequencing; overexpression; prevent; programs; protective effect; response; stem cell differentiation; stem cells; timeline; tissue regeneration; transcriptome; transcriptome sequencing

Abstract DHCR24 was first identified as a gene associated with cell aging and cell survival in Alzheimer’s disease. We recently found that Dhcr24 is transiently expressed in the mouse adrenal gland inner cortex which consists of aged adrenocortical cells that undergo apoptosis during development. We also found that thyroid hormone, which controls many developmental processes such as differentiation of retina in mammals and apoptosis during metamorphosis in amphibians, significantly upregulates Dhcr24 expression in the adrenal gland inner cortex. Interestingly, this upregulation of Dhcr24 is accompanied by the reduced apoptosis of aged adrenocortical cells. In this proposal, we aim to use our expertise in the adrenal gland and the next generation sequencing technique to study the connection between Dhcr24 and the thyroid hormone-mediated antiapoptotic effect in aged adrenocortical cells. In Aim 1, we will complete the initial phenotypic analysis of the Dhcr24 conditional knockout mice. This will decipher the role of Dhcr24 in the adrenal gland at the histological level. In Aim 2, we will compare transcriptomes in adrenal glands from Dhcr24 conditional knockout mice and wild type littermates before and after thyroid hormone treatment. This will identify Dhcr24 downstream genes and pathways associated with the thyroid hormone-mediated anti-apoptotic effect. Elucidating genes associated with Dhcr24 will advance our understanding of the Dhcr24-mediated anti-apoptotic effect. Identification of the thyroid hormone-responsive genes and their connections with Dhcr24 will help to understand how thyroid hormone and Dhcr24 influence cell survival and aging.

抽象的 DHCR24 首次被鉴定为与阿尔茨海默氏病细胞衰老和细胞存活相关的基因。我们 最近发现Dhcr24在小鼠肾上腺内皮质中瞬时表达，其组成为 老化的肾上腺皮质细胞在发育过程中发生凋亡。我们还发现甲状腺激素， 它控制许多发育过程，例如哺乳动物视网膜的分化和细胞凋亡 两栖动物的变态过程中，显着上调肾上腺内皮质中的 Dhcr24 表达。 有趣的是，Dhcr24 的上调伴随着衰老肾上腺皮质细胞凋亡的减少。 在这项提案中，我们的目标是利用我们在肾上腺和下一代测序方面的专业知识 研究 Dhcr24 与甲状腺激素介导的抗细胞凋亡之间关系的技术 对老化的肾上腺皮质细胞的作用。在目标 1 中，我们将完成 Dhcr24 的初始表型分析 条件敲除小鼠。这将在组织学水平上破译 Dhcr24 在肾上腺中的作用。在 目标 2，我们将比较 Dhcr24 条件敲除小鼠和野生型小鼠肾上腺的转录组 甲状腺激素治疗前后的同窝仔鼠。这将识别 Dhcr24 下游基因和 与甲状腺激素介导的抗凋亡作用相关的途径。阐明相关基因 Dhcr24 将增进我们对 Dhcr24 介导的抗凋亡作用的理解。甲状腺的识别 激素反应基因及其与 Dhcr24 的联系将有助于了解甲状腺激素如何 Dhcr24 影响细胞存活和衰老。