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Platycodin D regulates high glucose-induced ferroptosis of HK-2 cells through glutathione peroxidase 4 (GPX4).

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机构: [1]Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou City, Guangdong Province, China [2]Nephrotic Diagnosis And Treatment Center, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, China
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关键词: Diabetic nephropathy platycodin D HK-2 cells ferroptosis GPX4

摘要:
Diabetic nephropathy (DN) is associated with inflammation. Platycodin D (PD) demonstrates anti-inflammatory activity. However, whether PD affects DN remains to be explored. Here, we aimed to discuss the role of PD in DN and its underlying mechanisms. High glucose (HG)-induced HK-2 cells were treated with PD, and cell viability was assessed using the Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Ferroptosis-related factors such as lactate dehydrogenase (LDH) activity, lipid reactive oxygen species (ROS), iron (Fe2+) level, GSH level, and malondialdehyde (MDA) level were evaluated. Cell death was evaluated using the TUNEL assay. GPX4 expression was evaluated using Quantitative Real-time PCR (qRT-PCR) and Western blotting analysis. The results indicated that HG increased LDH activity, lipid ROS production, Fe2+ levels, and MDA levels and decreased GSH levels, suggesting that the HG condition induced ferroptosis. PD treatment inhibited ferroptosis in HG-induced cells, downregulated ACSL4 and TFR1 expression, and upregulated FTH-1 and SLC7A11 expression. PD reversed the effects of HG condition on cell death. Moreover, GPX4 expression was downregulated in HG-stimulated cells. Furthermore, we substantiated that PD suppressed ferroptosis by modulating GPX4 expression. In conclusion, PD inhibited ferroptosis in HG-induced HK-2 cells by upregulating GPX4 expression, suggesting that PD may be an effective drug for the clinical treatment of DN.

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出版当年[2021]版:
大类 | 4 区 生物学
小类 | 4 区 生物工程与应用微生物
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 生物工程与应用微生物
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第一作者机构: [1]Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou City, Guangdong Province, China
通讯作者:
通讯机构: [2]Nephrotic Diagnosis And Treatment Center, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, China [*1]The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No.1, Jingba Road, Jinan City, Shandong Province 250001, China
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