Am J Nephrol. 2018;47 Suppl 1:3-13. doi: 10.1159/000481633. Epub 2018 May 31.
Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement.
Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting.
足细胞生物学是一门正在发展的科学,有望帮助我们更好地理解与蛋白尿相关的多种疾病的发病机制。肾病综合征中的蛋白尿与涉及足细胞上皮细胞功能的肾小球机械功能障碍有关,包括足细胞足突融合。
成像技术的发展提高了我们对人类肾小球和皮质详细结构的认识。足细胞的足突附着在肾小球基底膜(GBM)上的肾小球毛细血管上,形成细胞间连接,形成裂孔隔膜过滤屏障,有助于维持正常的肾功能。该区域的损伤与肾小球疾病有关。受损的足细胞发生融合,失去结构并展开,导致滤过屏障功能降低。融合通常与局灶节段性肾小球硬化症、微小病变性肾病和糖尿病中的蛋白尿有关。据认为,这是由于足突细胞的肌动蛋白细胞骨架的破坏,复杂的收缩装置使足细胞能够根据滤过需求的变化进行动态重组。足细胞耗竭的过程与肾小球硬化和慢性肾脏病的发展相关。与 GBM 相互作用的黏着斑复合物将足细胞固定在肾小球结构内,防止其脱落。
对肾小球足细胞生物学的了解有助于我们深入理解肾小球过滤过程的科学和力学原理,为临床靶向治疗的各种新潜在应用开辟了道路。