Role of cathepsin L in idiopathic nephrotic syndrome in children
Role of cathepsin L in idiopathic nephrotic syndrome in children
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DOI：
10.1016/j.mehy.2020.109718
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发表时间：
2020-08-01
影响因子：
4.7
通讯作者：
Mitsuru, Okada
中科院分区：
文献类型：
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作者：
Keisuke, Sugimoto;Kohei, Miyazaki;Mitsuru, Okada
肾病综合征是儿童最常见的肾小球疾病之一。肾小球足细胞功能障碍可导致蛋白尿，即尿液中存在大量蛋白质。足细胞是独特的上皮细胞，分为3个独立的结构和功能部分：细胞体，主要过程和足突。由于突触足蛋白、发动蛋白和肌动蛋白是足细胞骨架的重要组成部分，这些蛋白的降解与细胞骨架的不稳定性有关，导致蛋白尿的发生。组织蛋白酶L（Cathepsin L，CatL）是一种半胱氨酸蛋白酶，在多种肾脏疾病中起着重要作用。在嘌呤霉素氨基糖苷诱导的肾病大鼠中，CatL表达升高，其用作微小变化NS的模型。在不发生蛋白尿的CatL缺陷小鼠中，发动蛋白通过CatL介导的分解逃逸而保留，导致足细胞的过滤屏障没有变化。然而，关于CatL在NS中的作用的信息有限。基于这些数据，CatL可能在蛋白尿的发生中起重要作用。此外，确定CatL的功能可能有助于更好地了解儿童期发病的NS的发病机制。我们推测高水平的CatL可导致足细胞的细胞骨架不稳定，从而导致儿童期发病的NS的蛋白尿。
Nephrotic syndrome (NS) is one of the most common glomerular diseases in children. Glomerular podocyte dysfunction can result in proteinuria, the presence of a large amount of protein in the urine. Podocytes are unique epithelial cells that divide into 3 separate structural and functional segments: a cell body, major processes, and foot processes. Since synaptopodin, dynamin, and actin are crucial components of the podocyte cytoskeleton, degradation of these proteins is associated with cytoskeleton instability, resulting in the development of proteinuria. Cathepsin L (CatL), a cysteine proteinase, plays a crucial role in various renal diseases. CatL expression is elevated in rats with puromycin aminonucleoside-induced nephropathy, which is used as a model of minimal change NS. In CatL-deficient mice, which do not develop proteinuria, dynamin is retained through the escape of CatL-mediated decomposition, resulting in no changes in the filtration barrier of podocytes. However, there is limited information on the roles of CatL in NS. Based on these data, CatL might play an important role in the development of proteinuria. Furthermore, identifying the functions of CatL may contribute to a better understanding of the pathogenesis of childhood-onset NS. We hypothesize that high levels of CatL can lead to cytoskeletal instability of podocytes, resulting in proteinuria in childhood-onset NS.