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

在西方世界，大约10%的成年人口受到慢性肾脏疾病的影响，而治疗方案很少，因此需要诱导肾脏再生的治疗方法。肾脏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，这些肾单位的丧失不可避免地导致肾功能的恶化。与哺乳动物不同，斑马鱼可以诱导干细胞再生肾单位，作为对肾脏损伤的反应。在斑马鱼中，在受伤时产生新的肾单位，导致新形成的肾单位与先前存在的肾脏结构整合，形成新的连接。这些新的肾脏系统功能齐全。在新肾单位的发育过程中，只有少数成分已被确定，启动新肾单位发育的机制在很大程度上是未知的。在这一研究金的范围内，需要确定这些机制，并进一步确定其特征。作为这些目标的基础，进行了单细胞RNA测序分析，从而确定了主要在斑马鱼干细胞种群中表达的基因。作为这些基因的例子，生长激素受体和白细胞介素6受体复合体可以被命名。这两种受体都通过转录因子STAT发挥调节功能。因此，检测上述受体在斑马鱼中的表达并分析其功能是我们的目标。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，即识别促进再生的机制。这些结果将用于改进药物疗法的开发，并允许在人体内进行生物肾脏的体外工程。

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.