SH3BP2在肾病综合征中作为免疫和非免疫细胞调节因子的新作用

Glomerular diseases Pub Date : 2024-11-19 eCollection Date: 2025-01-01 DOI:10.1159/000542703
Tarak Srivastava, Mukut Sharma
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引用次数: 0

摘要

背景:微小改变病(MCD)和局灶节段性肾小球硬化(FSGS)是肾病综合征的主要形式,仍然难以治疗。MCD和FSGS具有不同但又重叠的临床、组织学、代谢和分子特征。有效使用免疫抑制药物、激活免疫细胞、改变细胞因子谱和上调信号通路表明免疫功能障碍与肾病综合征之间存在联系,但免疫发病的确切机制尚不清楚。免疫功能障碍是一个正在进行的研究领域,以确定治疗肾病综合征的新分子靶点。然而,现有的动物模型并不能直接解决免疫功能障碍在肾病综合征中的作用。遗传分析表明,足细胞特异性蛋白相关的异质基因可能间接导致滤过屏障损伤,影响肾病综合征的发生和进展。SH3BP2蛋白通过其作为许多信号介质和酶的支架的作用来调节几种途径。SH3BP2在包括足细胞在内的免疫细胞和非免疫细胞中均有表达。在适应性和先天免疫系统的细胞和分子中讨论了SH3BP2的作用。综述了SH3BP2在肾病综合征以外疾病中的重要性及其在人肾病综合征免疫发病机制中的作用。我们概述了一种具有功能获得突变(Sh3bp2 KI/KI)的转基因小鼠品系的主要特征,作为研究肾病综合征免疫发病机制的潜在模型。关键信息:非受体、非催化蛋白如SH3BP2是一组调节肾病综合征先天和适应性免疫反应的新蛋白。新的证据表明SH3BP2在肾病综合征的免疫发病机制中起关键作用。我们最近的研究结果表明,具有功能获得突变的转基因小鼠(Sh3bp2 KI/KI)可能是研究肾病综合征免疫发病机制的独特模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Emerging Role of SH3BP2 as Regulator of Immune and Nonimmune Cells in Nephrotic Syndrome.

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are major forms of nephrotic syndrome that remain difficult to treat. MCD and FSGS have distinct but also overlapping clinical, histological, metabolic, and molecular features. Effective use of immunosuppressive drugs, activated immune cells, altered cytokine profiles, and upregulated signaling pathways suggest a link between immune dysfunction and nephrotic syndrome, but the exact mechanism of immunopathogenesis is unclear. Immune dysfunction is an area of ongoing research for identifying novel molecular targets for treating nephrotic syndrome. However, the available animal models do not directly address the role of immune dysfunction in nephrotic syndrome.

Summary: Genetic analysis indicates that heterogeneous genes related to the podocyte-specific proteins may indirectly cause damage to filtration barrier and influence the onset and progression of nephrotic syndrome. SH3BP2 protein regulates several pathways through its role as a scaffold for many signaling mediators and enzymes. SH3BP2 is expressed in immune as well as in nonimmune cells including podocytes. The role of SH3BP2 is discussed in the context of cells and molecules of adaptive and innate immune systems. Available information on the importance of SH3BP2 in diseases other than nephrotic syndrome and its role in the immunopathogenesis of human nephrotic syndrome are summarized. We outline the key features of a transgenic mouse strain with a gain-in-function mutation (Sh3bp2 KI/KI ) as a potential model to study immunopathogenesis of nephrotic syndrome.

Key messages: Non-receptor, non-catalytic proteins such as SH3BP2 are a novel group of proteins that regulate the innate and adaptive immune responses in nephrotic syndrome. New evidence suggests a critical role of SH3BP2 in immunopathogenesis of nephrotic syndrome. Our recent results demonstrate that transgenic mice (Sh3bp2 KI/KI ) with a gain-in-function mutation will likely be a unique model to study immunopathogenesis of nephrotic syndrome.

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