BACKGROUND The antibody against proteasome subunit alpha type 1 (PSMA1) is a podocyte autoantibody in idiopathic nephrotic syndrome (INS) children identified in our previous study. The aim of this study was to explore the characteristics of INS in children and the mechanism underlying its involvement in the development of INS. METHODS The levels of serum anti-PSMA1 autoantibodies in children were detected via protein microarray and compared among different disease groups. The recombinant PSMA1 protein was injected subcutaneously and intraperitoneally into mice to observe glomerular morphology and function. The PSMA1-knockdown and PSMA1-overexpressing cell lines were constructed from mouse podocytes, and their cytoskeleton and function were analyzed. Homozygous zebrafish with psma1 knockout were observed. RESULTS The levels of serum anti-PSMA1 autoantibodies were higher in INS children and varied with urinary protein. In mice immunized with PSMA1, the presence of serum anti-PSMA1 autoantibody caused albuminuria and damage to the glomerular filtration membrane. Deficiency of PSMA1 impaired the podocyte cytoskeleton and physiological function. Complete deletion of psma1 caused edema, abnormal glomerular morphology and effacement of foot processes in zebrafish. CONCLUSIONS PSMA1 played an important role in the maintenance of podocyte morphology and function.

中文翻译：

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在自身免疫性足细胞病中靶向蛋白酶体亚基 α 1 型的自身抗体。


背景 抗蛋白酶体亚基 α 1 型 （PSMA1） 的抗体是我们之前研究中发现的特发性肾病综合征 （INS） 儿童中的足细胞自身抗体。本研究旨在探讨儿童 INS 的特征及其参与 INS 发展的机制。方法 通过蛋白微阵列检测儿童血清抗 PSMA1 自身抗体水平，并在不同疾病组间进行比较。将重组 PSMA1 蛋白皮下和腹膜内注射到小鼠体内，观察肾小球形态和功能。从小鼠足细胞构建 PSMA1 敲低和 PSMA1 过表达细胞系，并分析其细胞骨架和功能。观察到 psma1 敲除的纯合斑马鱼。结果 INS 患儿血清抗 PSMA1 自身抗体水平较高，且随尿蛋白而变化。在用 PSMA1 免疫的小鼠中，血清抗 PSMA1 自身抗体的存在导致白蛋白尿和肾小球滤过膜损伤。PSMA1 的缺乏损害了足细胞细胞骨架和生理功能。psma1 的完全缺失导致斑马鱼水肿、肾小球形态异常和足突消失。结论 PSMA1 在维持足细胞形态和功能中起重要作用。