Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end‐stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies. Here, we present an FSGS‐like model in zebrafish larvae, an eligible vertebrate model for kidney research. In a transgenic zebrafish strain, podocytes were depleted, and the glomerular response was investigated by histological and morphometrical analysis combined with immunofluorescence staining and ultrastructural analysis by transmission electron microscopy. By intravenous injection of fluorescent high‐molecular weight dextran, we confirmed leakage of the size selective filtration barrier. Additionally, we observed severe podocyte foot process effacement of remaining podocytes, activation of proximal tubule‐like parietal epithelial cells identified by ultrastructural cytomorphology, and expression of proximal tubule markers. These activated cells deposited extracellular matrix on the glomerular tuft which are all hallmarks of FSGS. Our findings indicate that glomerular response to podocyte depletion in larval zebrafish resembles human FSGS in several important characteristics. Therefore, this model will help to investigate the disease development and the effects of potential drugs in a living organism.

中文翻译：

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斑马鱼幼虫长期足细胞耗竭类似于哺乳动物局灶性和节段性肾小球硬化症

局灶节段性肾小球硬化 (FSGS) 是一种常见于肾病综合征患者的组织学模式，通常会进展为终末期肾病。这种组织学定义实体的发展的第一步是损伤和最终耗尽足细胞，肾小球毛细血管上具有重要功能的肾小球滤过屏障的高度树枝状交叉细胞。由于仍然没有因果治疗选择，因此需要动物模型来开发新的治疗策略。在这里，我们在斑马鱼幼虫中展示了一个类似 FSGS 的模型，这是一种适合肾脏研究的脊椎动物模型。在转基因斑马鱼品系中，足细胞耗尽，通过组织学和形态计量学分析结合免疫荧光染色和透射电子显微镜超微结构分析研究肾小球反应。通过静脉注射荧光高分子量葡聚糖，我们证实了尺寸选择性过滤屏障的泄漏。此外，我们观察到剩余足细胞严重的足细胞足突消失，通过超微结构细胞形态学鉴定的近曲小管样壁上皮细胞的活化，以及近曲小管标志物的表达。这些活化的细胞将细胞外基质沉积在肾小球簇上，这些都是 FSGS 的标志。我们的研究结果表明，斑马鱼幼虫足细胞耗竭的肾小球反应在几个重要特征上类似于人类 FSGS。所以，