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- W4285491256 abstract "Abstract Background: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. In recent clinical trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) showed excellent renoprotection effects, but the underlying mechanism remains to be investigated. Previous studies have revealed an important role of ferroptosis, which is mediated by iron overload and lipid peroxidation, in the progression of DKD. Therefore, it is of interest to explore the effects of SGLT2i on ferroptosis in DKD due to its role in alleviating oxidative stress. Methods: Diabetic ( db/db) mice were administered with dapagliflozin or solvent treatment from 9 to 22 weeks of age, and were compared with non-diabetic (m/m) mice. High glucose/high fat (HG/HF) was applied to HK-2 cells, and effects of dapagliflozin on ferroptosis in HK-2 cells as well as the underlying mechanism were investigated. Results: Typical changes of ferroptosis including massive lipid peroxidation, reduced antioxidant capability, and iron overload were found in db/db mice and HG/HF treated HK-2 cells. Furthermore, increased expression of hypoxia‐inducible factor‐1α (HIF‐1α) and heme oxygenase-1 (HO1) was observed in db/db mice and HG/HF cultured cells as well. Dapagliflozin treatment significantly ameliorated the ferroptosis-related changes via inhibiting HIF‐1α/HO1 axis in vivo and in vitro . Besides, downregulation of HIF‐1α/HO1 axis rescued ferroptosis, while overexpression of HO1 aggravated ferroptosis induced by HG/HF in HK-2 cells. In DKD patients, the expression level of GPX4 in the kidney was significantly lower than that in healthy controls. Conclusion: SGLT2i play a renal protective effect, at least in parts, via inhibiting HIF‐1α/HO1 axis mediated ferroptosis." @default.
- W4285491256 created "2022-07-15" @default.
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- W4285491256 date "2022-07-15" @default.
- W4285491256 modified "2023-09-26" @default.
- W4285491256 title "Dapagliflozin alleviates diabetic kidney disease via HIF‐1α/HO1 mediated ferroptosis" @default.
- W4285491256 doi "https://doi.org/10.21203/rs.3.rs-1745222/v1" @default.
- W4285491256 hasPublicationYear "2022" @default.
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