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- Title
Quercetin Ameliorates Diabetic Kidney Injury by Inhibiting Ferroptosis via Activating Nrf2/HO-1 Signaling Pathway.
- Authors
Feng, Qi; Yang, Yang; Qiao, Yingjin; Zheng, Yifeng; Yu, Xiaoyue; Liu, Fengxun; Wang, Hui; Zheng, Bin; Pan, Shaokang; Ren, Kaidi; Liu, Dongwei; Liu, Zhangsuo
- Abstract
Diabetic nephropathy (DN) is thought to be the major cause of end-stage renal disease. Due to its complicated pathogenesis and the low efficacy of DN treatment, a deep understanding of new etiological factors may be useful. Ferroptosis, a nonapoptotic form of cell death, is characterized by the accumulation of iron-dependent lipid peroxides to lethal levels. Ferroptosis-triggered renal tubular injury is reported to participate in the development of DN, and blocking ferroptosis might be an effective strategy to prevent the development of DN. Quercetin (QCT), a natural flavonoid that is present in a variety of fruits and vegetables, has been reported to ameliorate DN. However, its underlying nephroprotective mechanism is unclear. Herein, we explored the antiferroptosic effect of QCT and verified its nephroprotective effect using DN mice and high glucose (HG)-incubated renal tubular epithelial cell models. We found HG-induced abnormal activation of ferroptosis of renal tubular epithelial cells, and QCT treatment inhibited ferroptosis by downregulating the expression of transferrin receptor 1 (TFR-1) and upregulating the expression of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH-1), and the cystine/glutamate reverse antiporter solute carrier family 7 member (SLC7A11) in DN mice and HG-incubated HK-2 cells. Subsequently, both in vitro and in vivo results confirmed that QCT activated the NFE2-related factor 2 (Nrf2)/Heme oxygenase-1(HO-1) signaling pathway by increasing the levels of Nrf2 and HO-1. Therefore, this study supports that QCT inhibits the ferroptosis of renal tubular epithelial cells by regulating the Nrf2/HO-1 signaling pathway, providing a novel insight into the protective mechanism of QCT in DN treatment.
- Subjects
CHINA; RNA analysis; GLUCOSE metabolism; STATISTICS; CELL culture; SEQUENCE analysis; STAINS &; staining (Microscopy); NUCLEAR factor E2 related factor; ANIMAL experimentation; ONE-way analysis of variance; IMMUNOHISTOCHEMISTRY; QUERCETIN; CELLULAR signal transduction; T-test (Statistics); CELL survival; ELECTRON microscopy; DESCRIPTIVE statistics; GENE expression profiling; EPITHELIAL cells; DATA analysis; POLYMERASE chain reaction; DIABETIC nephropathies; CELL death; MICE
- Publication
American Journal of Chinese Medicine, 2023, Vol 51, Issue 4, p997
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X23500465