Nagata Michio, Kobayashi Namiko, Hara Satoshi
Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba-City, Ibaraki, 305-8577, Japan.
Nephrology, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-850, Japan.
Pflugers Arch. 2017 Aug;469(7-8):983-988. doi: 10.1007/s00424-017-2023-x. Epub 2017 Jun 29.
Podocyte loss is the fundamental basis of glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) is a progressive glomerular disease, and its glomerular features are a prototype of podocyte loss-driven glomerulosclerosis. The glomerular pathology of FSGS is characterized by a focal and segmental location of the sclerotic lesions in human FSGS; segmental sclerosis often shows simultaneous intra- and extra-capillary changes, including parietal cell migration, capillary collapse, hyaline deposition, and intra-capillary thrombi and occasional hypercellularity. This suggests that local cellular events, initiated by podocyte loss, are the basis of the segmental lesions in FSGS. Using podocyte-specific injury by toxin administration, a series of recent works has identified the cellular basis of the glomerular response to podocyte loss. This review discusses the molecular pathway of the local response to podocyte loss and its progression to sclerosis. Recent results suggest that segmental sclerosis is a physiological tissue response aimed at halting protein leakage from a disrupted filtration barrier.
足细胞丢失是肾小球硬化的根本基础。局灶节段性肾小球硬化（FSGS）是一种进行性肾小球疾病，其肾小球特征是足细胞丢失驱动的肾小球硬化的典型代表。FSGS的肾小球病理特征在于人类FSGS中硬化病变的局灶性和节段性定位；节段性硬化常同时显示毛细血管内和毛细血管外的变化，包括壁层细胞迁移、毛细血管塌陷、透明样沉积、毛细血管内血栓形成以及偶尔的细胞增多。这表明由足细胞丢失引发的局部细胞事件是FSGS节段性病变的基础。通过给予毒素造成足细胞特异性损伤，最近的一系列研究确定了肾小球对足细胞丢失反应的细胞基础。本综述讨论了对足细胞丢失的局部反应及其进展为硬化的分子途径。最近的研究结果表明，节段性硬化是一种旨在阻止蛋白质从受损滤过屏障漏出的生理性组织反应。
