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

• Published in: Acta diabetologica 2024-02, Vol.61 (2), p.225-234
• Main Authors: Li, Xiang, Jiang, Xiao, Jiang, Mei, Wang, Zhi-feng, Zhao, Tao, Cao, Si-ming, Li, Qiu-Mei
• Format: Article
• Language: English
• Subjects: Animals; Caspase-1; Caspases - metabolism; Caspases - pharmacology; Cell viability; Diabetes; Glomerulus; GLP-1 receptor agonists; Glucagon; Glucagon-like peptide 1; Glucose; Glucose - metabolism; IL-1β; Inflammasomes; Inflammasomes - metabolism; Inflammasomes - pharmacology; Inflammation; Interleukin 18; Interleukin-18 - metabolism; Interleukin-18 - pharmacology; Internal Medicine; Liraglutide - pharmacology; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original Article; Podocytes; Pyroptosis; Renal function; Signal Transduction; Western blotting
• ISSN: 1432-5233; 0940-5429; 1432-5233
• DOI: 10.1007/s00592-023-02184-y

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.