Tian Xuefei, Bunda Patricia, Ishibe Shuta
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
Front Med (Lausanne). 2022 Feb 10;9:801837. doi: 10.3389/fmed.2022.801837. eCollection 2022.
Endocytosis is a mechanism that internalizes and recycles plasma membrane components and transmembrane receptors via vesicle formation, which is mediated by clathrin-dependent and clathrin-independent signaling pathways. Podocytes are specialized, terminally differentiated epithelial cells in the kidney, located on the outermost layer of the glomerulus. These cells play an important role in maintaining the integrity of the glomerular filtration barrier in conjunction with the adjacent basement membrane and endothelial cell layers within the glomerulus. An intact podocyte endocytic machinery appears to be necessary for maintaining podocyte function. pathologic human genetic mutations and loss-of-function studies of critical podocyte endocytosis genes in genetically engineered mouse models suggest that this pathway contributes to the pathophysiology of development and progression of proteinuria in chronic kidney disease. Here, we review the mechanism of cellular endocytosis and its regulation in podocyte injury in the context of glomerular diseases. A thorough understanding of podocyte endocytosis may shed novel insights into its biological function in maintaining a functioning filter and offer potential targeted therapeutic strategies for proteinuric glomerular diseases.
内吞作用是一种通过囊泡形成内化并循环质膜成分和跨膜受体的机制，其由网格蛋白依赖性和网格蛋白非依赖性信号通路介导。足细胞是肾脏中特化的终末分化上皮细胞，位于肾小球的最外层。这些细胞与肾小球内相邻的基底膜和内皮细胞层一起，在维持肾小球滤过屏障的完整性方面发挥着重要作用。完整的足细胞内吞机制似乎是维持足细胞功能所必需的。人类病理基因突变以及基因工程小鼠模型中关键足细胞内吞基因的功能丧失研究表明，该途径参与了慢性肾脏病蛋白尿发生发展的病理生理学过程。在此，我们综述了细胞内吞作用机制及其在肾小球疾病背景下对足细胞损伤的调节。深入了解足细胞内吞作用可能为其在维持有效滤过中的生物学功能提供新的见解，并为蛋白尿性肾小球疾病提供潜在的靶向治疗策略。
