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: 10372661
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372661
• 关键词: Adrenal Cortex; Adrenal Glands; Affect; Age; Aging; Alzheimer' s Disease; Amphibia; 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; Knock-out; Knockout Mice; Mammals; Mediating; Mediator of activation protein; Modeling; Mus; Neurons; Organism; Oxidative Stress; Pathway interactions; Phenotype; Pilot Projects; Prevention; Retina; Role; Techniques; Testing; Thyroid Gland; Thyroid Hormones; TimeLine; Tissues; Up-Regulation; abeta accumulation; adrenal cortex tumor; age related; aged; capsule; cell age; conditional knockout; differential expression; hormonal signals; mouse model; next generation sequencing; overexpression; prevent; programs; protective effect; response; stem; stem cells; 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.

摘要 DHCR 24最初被鉴定为与阿尔茨海默病中的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，其由以下组成： 衰老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， 其控制许多发育过程，例如哺乳动物视网膜的分化和在哺乳动物中的细胞凋亡。 在两栖动物的变态中，显著上调Dhcr24在肾上腺内皮质的表达。 有趣的是，Dhcr24的这种上调伴随着老年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 技术研究Dhcr24与甲状腺癌介导的抗凋亡之间的联系 对衰老肾上腺皮质细胞的影响。在目标1中，我们将完成Dhcr 24的初始表型分析， 条件性基因敲除小鼠这将在组织学水平上解释Dhcr24在肾上腺中的作用。在 目的2，我们将比较Dhcr24条件敲除小鼠和野生型小鼠肾上腺中的转录组 甲状腺激素治疗前后的同窝仔。这将鉴定Dhcr24下游基因， 与甲状腺癌介导的抗凋亡作用相关的途径。阐明与 Dhcr24的发现将进一步加深我们对Dhcr24介导的抗凋亡作用的理解。甲状腺的鉴别 甲状腺激素反应基因及其与Dhcr24的联系将有助于了解甲状腺激素和 Dhcr24影响细胞存活和衰老。