Inhibition of Caspase-3/GSDME Pathway-Mediated Pyroptosis of Renal Tubular Epithelial Cells by Dagliflozin in the Pathogenesis of Diabetic Kidney Disease and Study of Its Mechanism
Hong Jiang,1 Mengya Gao,1 Jiaqi Liu,2 Lijuan Yang,2 Lei Liu1 1Department of Nephrology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Physiology, Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-06-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Subjects: | |
| Online Access: | https://www.dovepress.com/inhibition-of-caspase-3gsdme-pathway-mediated-pyroptosis-of-renal-tubu-peer-reviewed-fulltext-article-DMSO |
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| Summary: | Hong Jiang,1 Mengya Gao,1 Jiaqi Liu,2 Lijuan Yang,2 Lei Liu1 1Department of Nephrology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Physiology, Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Lei Liu, Email bbmcll@163.comObjective: Investigating the effects and mechanisms of dapagliflozin on pyroptosis of renal tubular epithelial cells under high-glucose conditions through the regulation of the Caspase-3/GSDME signaling pathway, providing experimental evidence for the clinical treatment of diabetic kidney disease.Methods: Human renal tubular epithelial cells (HK-2) were cultured in vitro and divided into control group (5mmol/L D-glucose), high-glucose group (30mmol/L D-glucose), dagliflozin group (2.5μmol/L dagliflozin), and monoinhibitor group (20μmol/L caspase-1 inhibitor), dual inhibitor group (20μmol/L caspase-1 inhibitor + 50μmol/L caspase-3 inhibitor), and SiRNA transfection group. All groups were intervened for 48h. The cell viability was detected by cell counting kit-8 and the glucose and dagliflozin concentrations of the intervention were determined. Caspase-1, caspase-3, GSDMD, GSDME, GSDME-N, caspase-8, NF-κB were detected by Western blot. Detection of cellular pyroptosis in each group by flow cytometry.Results: Compared with the control group, the D-glucose group showed decreased cell viability, increased cell pyroptosis, and increased levels of caspase-1, caspase-3, GSDMD, GSDME, GSDME-N, caspase-8, NF-κB, and other related proteins (P< 0.05). Compared with the D-glucose group, the rate of cellular pyroptosis and the levels of caspase-1, caspase-3, GSDMD, GSDME, GSDME-N and other related proteins were decreased in the dagliflozin group and the dual inhibitor group (P< 0.05). Compared with the transfected control group, the cellular pyroptosis rate and the levels of caspase-1, caspase-3, GSDMD, GSDME, GSDME-N, and other related proteins were then further reduced in the transfected group targeting SGLT2 knockdown (P< 0.05).Conclusion: In the proximal tubular cells of diabetic kidney disease, dagliflozin inhibited high glucose-induced pyroptosis of human HK-2, and its mechanism of action may be related to the inhibition of caspase 3/GSDME pathway signaling.Keywords: diabetic kidney disease, renal tubular epithelial cells, dagliflozin, pyroptosis |
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| ISSN: | 1178-7007 |