Non-steroidal mineralocorticoid receptor antagonist finerenone ameliorates diabetic nephropathy via suppressing SLC7A11-mediated ferroptosis.

Diabetic nephropathy (DN) is a severe complication of diabetes with high prevalence, and ferroptosis plays a key role in diabetic tubulopathy. Finerenone (FIN), a non-steroidal mineralocorticoid receptor antagonist, exerts renal protective effects, but its mechanism via regulating SLC7A11-mediated ferroptosis remains unclear. This study aimed to explore whether FIN ameliorates DN by suppressing SLC7A11-related ferroptosis. In vivo experiments used db/db diabetic mice (divided into control, DN model, and FIN-treated groups) and in vitro experiments used HK-2 cells exposed to high glucose (HG) with/without FIN. SLC7A11 was silenced via shRNA. Histological staining, Western blot, RT-qPCR, and biochemical assays detected fibrosis/ferroptosis markers. DN patients and db/db mice showed increased renal fibrosis and ferroptosis. FIN treatment alleviated renal tubular atrophy, fibrosis, and inflammatory infiltration in db/db mice, upregulated SLC7A11/GPX4, and restored GSH/MDA balance. In HG-induced HK-2 cells, FIN enhanced cell viability, reduced fibrosis, and suppressed ferroptosis by increasing SLC7A11/FTH1/GPX4 and decreasing lipid peroxidation/Fe²⁺. Silencing SLC7A11 reversed FIN's protective effects. Finerenone ameliorates DN by inhibiting SLC7A11-mediated ferroptosis, providing a novel mechanism for its renal protective effects and identifying potential therapeutic targets for DN management.