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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
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Dapagliflozin Alleviates Diabetic Kidney Disease
Yi-Hui Wang1,2, Dong-Yuan Chang1,3, Ming-Hui Zhao1,2,3
1Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
Antioxidants & Redox Signaling
|June 5, 2023
Summary
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) alleviate diabetic kidney disease by reducing ferroptosis. This study shows SGLT2i protects kidneys by targeting the HIF1α/HO1 pathway, mitigating oxidative stress and renal injury.
Area of Science:
- Nephrology
- Endocrinology
- Cellular Biology
Background:
- Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease.
- Sodium-glucose cotransporter 2 inhibitors (SGLT2i) offer renoprotection, but mechanisms are unclear.
- Ferroptosis, linked to oxidative stress, is implicated in DKD progression.
Purpose of the Study:
- To investigate if SGLT2i can alleviate ferroptosis and renal injury in DKD.
- To explore the role of the HIF1α/HO1 axis in SGLT2i-mediated renoprotection.
Main Methods:
- Utilized db/db mice and high glucose/high fat (HG/HF)-treated HK-2 cells to model DKD.
- Assessed ferroptosis markers, oxidative stress, and iron levels.
- Examined the expression of hypoxia inducible factor 1α (HIF1α) and heme oxygenase 1 (HO1) and the effect of dapagliflozin.
Main Results:
- DKD models exhibited ferroptosis markers, including lipid peroxidation, reduced antioxidant capacity, and iron overload.
- Increased HIF1α and HO1 expression was observed in DKD models.
- Dapagliflozin treatment attenuated ferroptosis and HIF1α/HO1 axis activation.
- Manipulating HIF1α/HO1 levels affected ferroptosis in HK-2 cells.
Conclusions:
- SGLT2i exert renoprotective effects in DKD, partly by inhibiting ferroptosis.
- The HIF1α/HO1 pathway is a key mediator of ferroptosis in DKD.
- Targeting ferroptosis via the HIF1α/HO1 axis represents a potential therapeutic strategy for DKD.
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