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High glucose elevates intracellular calcium level and induces ferroptosis in glomerular endothelial cells through the miR-223-3p/ITPR3 pathway

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机构: [1]Department of Endocrinology, The Third Clinical Medical College of China Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang, 443002, Hubei, China [2]Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, 650031, China [3]Department of Radiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650031, China
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关键词: miR-223-3p ITPR3 High glucose-stimulated Ferroptosis Intracellular calcium ions

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We investigated the link between ferroptosis and the miR-223-3p/inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) pathway in diabetic kidney disease (DKD). Blood samples from DKD patients and healthy controls were analysed for iron ions, calcium ions, and lipid peroxidation. High-glucose-induced glomerular endothelial cells were used to simulate DKD. MiR-223-3p overexpression or silencing was achieved using adenoviruses, affecting ferroptosis regulators (glutathione peroxidase 4 [GPX4], cystine/glutamate transporter (xCT), and long-chain acyl-CoA synthetase 4 [ACSL4]) and ITPR3. DKD patients showed elevated levels of iron ions, calcium ions, and lipid peroxidation. High glucose downregulated miR-223-3p, reducing xCT and GPX4 expression and increasing ACSL4 expression. MiR-223-3p was confirmed to target ITPR3 through luciferase reporter assay. MiR-223-3p overexpression reversed high-glucose-induced effects on ferroptosis markers and ITPR3 expression. In summary, high glucose levels decreased miR-223-3p expression, leading to increased calcium ion levels and ferroptosis, potentially through ITPR3 modulation. These findings provide insights into the mechanisms underlying DKD and its potential therapeutic targets.Copyright © 2024 Elsevier B.V. All rights reserved.

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大类 | 3 区 医学
小类 | 3 区 内分泌学与代谢 3 区 细胞生物学
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Q2 CELL BIOLOGY Q2 ENDOCRINOLOGY & METABOLISM

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第一作者机构: [1]Department of Endocrinology, The Third Clinical Medical College of China Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang, 443002, Hubei, China [2]Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, 650031, China
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