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

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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.