Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands.
Nephrol Dial Transplant. 2022 Sep 22;37(10):1808-1815. doi: 10.1093/ndt/gfab016.
Nephrotic syndrome (NS) is characterized by massive proteinuria; podocyte loss or altered function is a central event in its pathophysiology. Treatment with glucocorticoids is the mainstay of therapy, however, many patients experience one or multiple relapses and prolonged use may be associated with severe adverse effects. Recently the beneficial effects of glucocorticoids have been attributed to a direct effect on podocytes in addition to the well-known immunosuppressive effects. The molecular effects of glucocorticoid action have been studied using animal and cell models of NS. This review provides a comprehensive overview of different molecular mediators regulated by glucocorticoids, including an overview of the model systems that were used to study them. Glucocorticoids are described to stimulate podocyte recovery by restoring pro-survival signalling of slit diaphragm-related proteins and limiting inflammatory responses. Of special interest is the effect of glucocorticoids on stabilizing the cytoskeleton of podocytes, since these effects are also described for other therapeutic agents used in NS, such as cyclosporin. Current models provide much insight but do not fully recapitulate the human condition since the pathophysiology underlying NS is poorly understood. New and promising models include the glomerulus-on-a-chip and kidney organoids, which have the potential to be further developed into functional NS models in the future.
肾病综合征（NS）的特征是大量蛋白尿；足细胞丧失或功能改变是其病理生理学的中心事件。糖皮质激素治疗是主要的治疗方法，然而，许多患者经历一次或多次复发，且长期使用可能与严重不良反应相关。最近，糖皮质激素的有益作用除了众所周知的免疫抑制作用外，还归因于对足细胞的直接作用。使用 NS 的动物和细胞模型研究了糖皮质激素作用的分子效应。这篇综述提供了一个全面概述了不同的分子介质受糖皮质激素调节，包括用于研究它们的模型系统概述。糖皮质激素被描述为通过恢复与裂孔隔膜相关蛋白的促生存信号和限制炎症反应来刺激足细胞的恢复。特别有趣的是糖皮质激素对稳定足细胞细胞骨架的作用，因为这些作用也被描述为用于 NS 的其他治疗剂，如环孢素。目前的模型提供了很多的见解，但不能完全重现人类的情况，因为 NS 的病理生理学还不清楚。新的有前途的模型包括在芯片上的肾小球和肾类器官，它们有可能在未来进一步发展成为功能性 NS 模型。
