Advanced glycated end-products modified transferrin mediates oxidative stress and ferroptosis in podocytes via advanced glycation end-product receptor in vitro

作者：Pingping Zhao, Binjing Pan, Jie Gao, Xiaoyu Lv, Yirong Wang, Jingfang Liu · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-22984-2 · 被引用次数：1 · 研究领域：Advanced Glycation End Products research、Ferroptosis and cancer prognosis、Chronic Kidney Disease and Diabetes

Previous studies have found the increased levels of transferrin (Tf) modified by advanced-glycation-end-products (AGE-Tf) in the serum of patients with type 2 diabetes mellitus and the kidneys of diabetic rats. The study aimed to investigate the effects of AGE-Tf on human podocytes in vitro. AGE-Tf was prepared by incubating Tf with different concentrations of glucose (0 mM, 5.6 mM, 11.1 mM, and 33.3 mM) in vitro. Podocytes were treated with AGE-Tf produced at different concentrations of glucose, and rescue experiments include AGE-Tf + deferoxamine mesylate (DFO), AGE-Tf + Ferrostatin-1 (Fer-1, inhibitors of ferroptosis), and AGE-Tf + advanced glycation end-product receptor (RAGE) antagonist peptide (RAP) groups. The total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO), and malonic dialdehyde (MDA) were measured, and the expression levels of glutathione peroxidase 4 (GPX4), acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4), and nuclear factor erythroid 2-related factor 2 (NRF2) were analyzed. In vitro, with increasing glucose levels, the degree of glycation of Tf increased gradually, and the total iron binding capacity decreased gradually. When podocytes were treated by AGE-Tf, podocyte activity decreased, and apoptosis increased. Antioxidant capacity decreased, and LPO and ROS levels increased. The expression of GPX4, NRF2, and SLC7A11 was down-regulated; the expression of ACSL4 was up-regulated. Wherea...