Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
Acta Physiol (Oxf). 2022 Aug;235(4):e13850. doi: 10.1111/apha.13850. Epub 2022 Jun 28.
Selective glomerular filtration relies on the membrane separating the glomerular arterioles from the Bowman space. As a major component of the glomerular filtration barrier, podocytes form foot processes by the actin cytoskeleton, which dynamically adjusts in response to environmental changes to maintain filtration barrier integrity. The slit diaphragms bridge the filtration slits between neighboring foot processes and act as signaling hubs interacting with the actin cytoskeleton. Focal adhesions relay signals to regulate actin dynamics while allowing podocyte adherence to the basement membrane. Mutations in actin regulatory and signaling proteins may disrupt the actin cytoskeleton, resulting in foot process retraction, effacement, and proteinuria. Large-scale gene expression profiling platforms, transgenic animal models, and other in vivo gene delivery methods now enhance our understanding of the interactions among podocyte focal adhesions, slit diaphragms, and actin dynamics. In addition, our team found that at least 66% of idiopathic nephrotic syndrome (INS) children have podocyte autoantibodies, which was defined as a new disease subgroup-, autoimmune podocytopathies. This review outlines the pathophysiological mechanisms of podocyte cytoskeleton protein interactions in proteinuria and glomerular podocytopathy.
选择性肾小球滤过依赖于将肾小球小动脉与鲍曼空间分隔开的膜。作为肾小球滤过屏障的主要组成部分，足细胞通过肌动蛋白细胞骨架形成足突，这些足突通过动态调整以响应环境变化来维持滤过屏障的完整性。裂孔隔膜连接相邻足突之间的滤过裂隙，并作为与肌动蛋白细胞骨架相互作用的信号枢纽。黏附斑将信号转导至肌动蛋白动力学，同时允许足细胞黏附于基膜。肌动蛋白调节蛋白和信号蛋白的突变可能会破坏肌动蛋白细胞骨架，导致足突回缩、消失和蛋白尿。大规模基因表达谱分析平台、转基因动物模型和其他体内基因传递方法现在增强了我们对足细胞黏附斑、裂孔隔膜和肌动蛋白动力学之间相互作用的理解。此外，我们的团队发现，至少 66%的特发性肾病综合征 (INS) 患儿存在足细胞自身抗体，这被定义为一种新的疾病亚组——自身免疫性足细胞病。本综述概述了蛋白尿和肾小球足细胞病中足细胞细胞骨架蛋白相互作用的病理生理机制。
