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GLP-1RAs inhibit the activation of the NLRP3 inflammasome signaling pathway to regulate mouse renal podocyte pyroptosis

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Abstract

Objective

Podocytes are closely related to renal function as an important part of the glomerulus. The reduction and damage of podocytes lead to further decline of renal function and aggravate the progression of DKD. Glucagon-like peptide-1 receptor agonists (GLP-1RAS) have recently attracted great attention in improving podocyte dysfunction, but the specific mechanism remains uncertain.

Methods

We used mouse kidney podocyte MPC5 to construct a high-glucose injury model. Cell viability was detected by the MTT method; RT-qPCR and western blotting were used to detect the expressions of NF-κB p65, NLRP3, GSDMD, N-GSDMD, caspase-1 and cleaved-caspase-1, and we used ELISA to detect the expressions of inflammatory factors IL-1β and IL-18.

Results

Our results showed that high glucose decreased podocyte survival, while liraglutide and semaglutide increased podocyte survival under high glucose. Liraglutide and semaglutide can inhibit the expression of pyroptosis-related genes and proteins and also inhibit the expression of inflammatory factors IL-1β, IL-18 increase.

Conclusion

The protective effect of liraglutide and semaglutide on podocytes may be achieved by regulating the NLRP3 inflammasome pathway and inhibiting pyroptosis, and there were no significant differences between the two GLP-1RAs (liraglutide and semaglutide) in inhibiting podocyte pyroptosis.

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Data availability

The datasets supporting the conclusions of this article are included within the article (and its additional files).

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Funding

This research was supported by the Medical Research Project Fund of Dalian Municipal Medical and Health Institutions:2211041.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolic Diseases, Dalian University Affiliated Xinhua Hospital, Dalian, 116021, Liaoning, China

    Xiang Li, Xiao Jiang, Mei Jiang, Zhi-feng Wang, Tao Zhao, Si-ming Cao & Qiu-Mei Li

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  1. Xiang Li
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  2. Xiao Jiang
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  3. Mei Jiang
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  5. Tao Zhao
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Contributions

Q-ML conceived and designed the study. XL and XJ conducted most of the experiments and data analysis, and wrote the manuscript. MJ, Z-FW, TZ, and S-MC participated in collecting data and helped to draft the manuscript. All authors reviewed and approved the manuscript.

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Correspondence to Qiu-Mei Li.

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This article belongs to the Topical Collection “Diabetic Nephropathy”, managed by: Giuseppe Pugliese.

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Li, X., Jiang, X., Jiang, M. et al. GLP-1RAs inhibit the activation of the NLRP3 inflammasome signaling pathway to regulate mouse renal podocyte pyroptosis. Acta Diabetol 61, 225–234 (2024). https://doi.org/10.1007/s00592-023-02184-y

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