Ferroptosis Mediates the Progression of Hyperuricemic Nephropathy by Activating RAGE Signaling

• DOI: 10.1089/ars.2024.0672
• Publication Date: 2025-03-10T09:02:06Z
• Authors: Qiang Wang; Yuemei Xi; Hairong Zhao; De Xie; Linqian Yu; Yunbo Yan; Jiayu Chen; Qian Zhang; Meng Liang; Jidong Cheng
• Keywords: RAGE

Aims: Hyperuricemic nephropathy (HN) represents a prevalent complication of hyperuricemia, typified by tubular dysfunction, inflammation, and progressive renal fibrosis with unclear mechanisms. Ferroptosis, an iron-dependent regulated cell death, is implicated in multiple diseases, but has rarely been linked to HN. In this study, we aim explore the possible role ferroptosis HN its underlying Results: We showed that urate oxidase knockout mice, model exhibited impairment elevated uric acid, creatinine, blood urea nitrogen levels, accompanied increased iron deposition decreased glutathione peroxidase 4 (GPX4) xCT expressions, suggesting involvement. Ferroptosis inhibitor Ferrostatin-1 (Fer-1) ameliorated injury, inflammatory infiltration, these mice. Mechanistically, Fer-1 restored antioxidant protein normalized ferroptosis-associated diminished overload lipid peroxidation, suppressed markers mitogen-activated kinase signaling. vitro, monosodium crystals induced human kidney 2 cells, characterized peroxidation accumulation. Notably, receptor for advanced glycation end products (RAGE) inhibition alleviated albeit without directly diminishing ferroptosis. These findings were validated hyperuricemia-related disease samples showing deposition, GPX4, RAGE expression. Innovation Conclusion: This study suggests may play development HN, potentially mediated through While improved it did not affect ferroptosis, indicating complex context-dependent injury. highlight associated pathways, including signaling, as potential therapeutic targets Antioxid. Redox Signal. 00, 000-000.