Role of cathepsin L in idiopathic nephrotic syndrome in children

Sugimoto Keisuke, Miyazaki Kohei, Enya Takuji, Miyazawa Tomoki, Morimoto Yuichi, Oshima Rina, Takemura Tsukasa, Okada Mitsuru
2020 Medical Hypotheses  
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
more » ... iated 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.
doi:10.1016/j.mehy.2020.109718 pmid:32289645 fatcat:o2brh6w25jgpjlpsio76rcwinq