Abstract：
Ferroptosis is a non-apoptotic form of cell death, involved in chronic kidney diseases (CKD) and acute kidney injury (AKI), so far, the role of ferroptosis in focal segmental glomerulosclerosis (FSGS) remains largely unknown. We aimed to investigate the role of ferroptosis in FSGS, in this study, we found the reduced expression of GPX4 in podocytes, as well as tubular epithelial cells (TECs), from patients with FSGS. Treatment with ferrostatin-1 (Fer-1), a potent and selective ferroptosis inhibitor, significantly reduced proteinuria, prevented glomerulosclerosis, attenuated podocyte injury in ADR-induced FSGS murine model. As expected, ADR treatment caused downregulation of GPX4 in human podocytes, treatment with Fer-1 greatly blocked the downregulation of GPX4, restored the GSH level and attenuated cell death. Furthermore, Fer-1 treatment greatly delayed the development of tubulointerstitial fibrosis in ADR-induced FSGS murine model. Taken together, ferroptosis is involved in the pathogenesis of FSGS, targeting ferroptosis is a promising therapeutic option for patients with FSGS.
摘要：
Ferroptosis是细胞死亡的非凋亡形式，参与慢性肾脏疾病（CKD）和急性肾损伤（AKI），到目前为止,铁性凋亡在局灶节段性肾小球硬化(FSGS)中的作用目前尚不清楚.我们的目的是研究FSGS中铁死亡的作用，在这项研究中，我们发现GPX4在足细胞中的表达减少，以及肾小管上皮细胞（TECs），FSGS患者用Fer-1(Fer-1)治疗，一种有效和选择性的铁凋亡抑制剂，显著减少蛋白尿，预防肾小球硬化，减轻ADR诱导的FSGS小鼠模型的足细胞损伤。不出所料,ADR治疗导致人足细胞中GPX4的下调，用Fer-1处理极大地阻断了GPX4的下调，恢复了GSH水平并减轻了细胞死亡。此外，Fer-1治疗大大延缓了ADR诱导的FSGS小鼠模型肾小管间质纤维化的发展。一起来看,FSGS的发病机制涉及铁性凋亡，靶向铁性凋亡是FSGS患者有希望的治疗选择.
