Dapagliflozin alleviates renal podocyte pyroptosis via regulation of the HO‑1/NLRP3 axis

Zhang,Zhenwang; Ni,Ping; Tang,Mingqiu; Song,Yi; Liu,Chao; Zhao,Baoqing

doi:10.3892/mmr.2023.13087

Dapagliflozin alleviates renal podocyte pyroptosis via regulation of the HO‑1/NLRP3 axis

Authors:
- Zhenwang Zhang
- Ping Ni
- Mingqiu Tang
- Yi Song
- Chao Liu
- Baoqing Zhao
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Affiliations: Medicine Research Institute and Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning, Hubei 437000, P.R. China, School of Clinical Medicine, Hubei University of Science and Technology, Xianning, Hubei 437000, P.R. China, School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei 437000, P.R. China
Published online on: September 8, 2023 https://doi.org/10.3892/mmr.2023.13087
Article Number: 200
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy is one of the most significant complications of diabetes, resulting in increased patient mortality. Dapagliflozin is an inhibitor of sodium‑glucose cotransporter 2 that has an important protective effect on the kidney. Recent studies showed that pyroptosis is involved in the advancement of diabetic nephropathy (DN). However, the potential molecular mechanisms underlying the association between pyroptosis and renal podocyte injury in DN remain unclear. Thus, the present study investigated the anti‑pyroptotic function of dapagliflozin in podocytes and further clarified the potential mechanisms. In this study, a model of lipid metabolism disturbance was established through palmitic acid (PA) induction in a mouse podocyte clone 5 (MPC5) cell line. MPC5 PA‑induced pyroptosis was measured by ELISA, western blotting, quantitative PCR and Hoechst 33342/propidium iodide double‑fluorescence staining. The protective role of HO‑1 was measured using knockdown and overexpression experiments. It was found that dapagliflozin attenuated the expression of pyroptosis‑related proteins, including nucleotide oligomerization domain‑like receptor thermal protein domain associated protein 3, apoptosis‑associated speck‑like protein containing a caspase activation and recruitment domain, caspase‑1, IL‑18 and IL‑1β in the PA group. Meanwhile, the heme oxygenase 1 (HO‑1) expression level decreased within PA, an effect that was reversed by dapagliflozin. Furthermore, the expression of pyroptosis‑related proteins and inflammatory cytokines was reduced following HO‑1 overexpression. Therefore, these results suggested that dapagliflozin ameliorates MPC5 pyroptosis by mediating HO‑1, which has a protective effect on diabetic nephropathy.

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