Characterizing the role of growth hormone and interleukin 6 expression for kidney regeneration in gentamicin-induced kidney injury in zebrafish

表征生长激素和白细胞介素 6 表达对庆大霉素诱导的斑马鱼肾损伤中肾脏再生的作用

• 批准号: 444273025
• 负责人: Dr. Heiko Schenk
• 金额: --
• 依托单位: Mount Desert Island Biological Laboratory
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/444273025?language=en
• 关键词: Characterizing; role; growth; hormone; interleukin

In the western world, approximately 10 % of the adult population is affected by chronic kidney disease, while therapeutic options are sparse, therefore, treatments that induce kidney regeneration are required. The central functional unit of the kidney is the nephron. Mammals are not able to induce regeneration of nephrons. As a consequence, the loss of those nephrons leads inevitably to the worsening of the kidney function. In contrast to mammals, zebrafish can induce nephron regeneration from stem cells as a response to kidney injury. In zebrafish, the generation of new nephrons upon injury results in the integration of newly formed nephrons to pre-existing kidney structures forming new connections. These new nephrons are fully functional. Only a few components in the development of new nephrons have been identified, the mechanisms to initiate the development of new nephrons are largely unknown. Within the scope of this fellowship, these mechanisms need to be identified and further characterized. As the basis for these aims, single-cell RNA sequencing analyses have been carried out leading to the identification of genes primarily expressed in the stem cell population of zebrafish. As examples for these genes, the growth hormone receptor and the Interleukin 6 receptor complex can be named. Both receptors exert their regulatory function via the transcription factor STAT. Therefore, it is our goal to detect the expression of the aforementioned receptors and analyze their function in zebrafish. Additionally, we aim to evaluate how kidney regeneration in zebrafish can be influenced by pharmacological substances to achieve our final goal, the identification of the mechanism that enhances regeneration. These results shall be used to improve the development of pharmacological therapies and to allow the in vitro engineering of a biological kidney in humans.

在西方世界，大约10%的成年人受到慢性肾脏疾病的影响，而治疗选择很少，因此，需要诱导肾脏再生的治疗。肾的中心功能单位是肾单位。哺乳动物不能诱导肾单位的再生。因此，这些肾单位的损失不可避免地导致肾功能的恶化。与哺乳动物相反，斑马鱼可以诱导干细胞再生肾单位作为对肾损伤的反应。在斑马鱼中，损伤后新肾单位的产生导致新形成的肾单位与预先存在的肾结构整合，形成新的连接。这些新的肾单位功能齐全。新肾单位发育过程中只有少数组分被鉴定，启动新肾单位发育的机制在很大程度上是未知的。在本研究金范围内，需要确定这些机制并进一步说明其特点。作为这些目标的基础，已经进行了单细胞RNA测序分析，从而鉴定出主要在斑马鱼干细胞群体中表达的基因。作为这些基因的实例，可以命名生长激素受体和白细胞介素6受体复合物。这两种受体通过转录因子STAT发挥其调节功能。因此，我们的目标是检测上述受体在斑马鱼中的表达并分析其功能。此外，我们的目标是评估药理物质如何影响斑马鱼的肾脏再生，以实现我们的最终目标，即确定增强再生的机制。这些结果将用于改善药理学疗法的开发，并允许在人体内进行生物肾脏的体外工程。