Cunanan Joanna, Zhang Daniel, Peired Anna Julie, Barua Moumita
Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Front Cell Dev Biol. 2025 Apr 24;13:1564847. doi: 10.3389/fcell.2025.1564847. eCollection 2025.
Podocytes are highly specialized, terminally differentiated cells in the glomerulus of the kidney and these cells play a central role in blood filtration. In this review, we comprehensively describe the cell biology of podocytes under healthy conditions and in glomerular disorders wherein podocyte injury is a major pathological mechanism. First, the molecular mechanisms that maintain podocyte actin cytoskeleton structure, permanent cell cycle exit, and metabolism under healthy conditions are described. Secondly, the mechanisms of podocyte injury, including genetic alterations and external insults that ultimately disrupt podocyte actin cytoskeleton dynamics or interrupt podocyte quiescence and mitochondrial metabolism are discussed. This understanding forms the basis of described potential therapeutic agents that act by modulating dysregulated podocyte cytoskeleton organization, prevent or reverse cell cycle re-entry, and re-establish normal mitochondrial energy production. Lastly, the application of modern techniques such as single cell RNA sequencing, super resolution microscopy, atomic force microscopy, and glomerular organoids is improving the resolution of mechanistic podocytopathy knowledge. Taken together, our review provides critical insights into the cellular and molecular mechanisms leading to podocyte loss, necessary for the advancement of therapeutic development in glomerular diseases.
足细胞是肾脏肾小球中高度特化的终末分化细胞，这些细胞在血液滤过中起核心作用。在本综述中，我们全面描述了健康状态下以及以足细胞损伤为主要病理机制的肾小球疾病中足细胞的细胞生物学。首先，描述了在健康条件下维持足细胞肌动蛋白细胞骨架结构、永久退出细胞周期和代谢的分子机制。其次，讨论了足细胞损伤的机制，包括最终破坏足细胞肌动蛋白细胞骨架动力学或中断足细胞静止和线粒体代谢的基因改变和外部损伤。这种认识构成了所述潜在治疗药物的基础，这些药物通过调节失调的足细胞细胞骨架组织、预防或逆转细胞周期重新进入以及重新建立正常的线粒体能量产生来发挥作用。最后，单细胞RNA测序、超分辨率显微镜、原子力显微镜和肾小球类器官等现代技术的应用正在提高对机械性足细胞病知识的解析度。综上所述，我们的综述为导致足细胞丢失的细胞和分子机制提供了关键见解，这对于肾小球疾病治疗发展的推进至关重要。
