Characterization of ferroptosis in kidney tubular cell death under diabetic conditions

• DOI: 10.1038/s41419-021-03452-x
• Publication Date: 2021-02-08T21:31:35Z
• Authors: Seonghun Kim; Shin-Wook Kang; Jeongho Joo; Seung Hyeok Han; Huiyoon Shin; Bo Young Nam; Jimin Park; Tae-Hyun Yoo; Gyuri Kim; Pureunchowon Lee; Jung Tak Park
• Keywords: GPX4; Pyroptosis

Abstract Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in under conditions. Recently, ferroptosis, an atypical form iron-dependent death, was reported cause kidney disease, including acute injury. Ferroptosis primed lipid peroxide accumulation through the cystine/glutamate antiporter system X c − (xCT) glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim this study evaluate role ferroptosis diabetes-induced TGF-β1-stimulated proximal epithelial cells mice models were used for vitro vivo experiments, respectively. xCT GPX4 expression, viability, concentration, peroxidation quantified indicate ferroptosis. effect inhibition assessed. In biopsy samples from patients, mRNA expression decreased compared nondiabetic samples. cells, intracellular concentration reduced enhanced, both which related ferroptosis-related death. Ferrostatin-1 (Fer-1), inhibitor, alleviated TGF-β1-induced mice, protein expressions control. decreased, while increased these changes Fer-1 treatment. could be therapeutic option nephropathy.