Epigallocatechin-3-gallate attenuates oxidative stress and apoptosis in podocytes of focal segmental glomerulosclerosis

Abstract

Abstract Focal segmental glomerulosclerosis (FSGS) is a major pathological feature of kidney injury, with limited therapeutic options currently available. This study aims to investigate the core mechanisms of podocyte injury in FSGS and the therapeutic potential of the natural extract epigallocatechin-3-gallate (EGCG). Through single-nucleus RNA sequencing of kidney tissues from patients with primary FSGS and an adriamycin (ADR)-induced nephropathy mouse model, we identified a subpopulation of injured podocytes. We found that damaged podocytes exhibited significantly elevated reactive oxygen species (ROS) levels and increased apoptotic activity compared to healthy podocytes. In animal experiments, EGCG treatment effectively reduced the elevation of the urine albumin-to-creatinine ratio, significantly alleviated glomerulosclerosis, and attenuated the ADR-induced decrease in the reduced glutathione/oxidized glutathione ratio in both serum and renal tissues of ADR-treated mice. Furthermore, in vitro treatment of conditionally immortalized mouse podocyte clone 5 confirmed that EGCG significantly reduced ADR-induced ROS production and apoptosis. These findings suggest that EGCG may provide a promising therapeutic approach for alleviating podocyte injury and mitigating FSGS progression.