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

当前位置： X-MOL 学术 › Acta Diabetol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

GLP-1RAs inhibit the activation of the NLRP3 inflammasome signaling pathway to regulate mouse renal podocyte pyroptosis
Acta Diabetologica ( IF 3.1 ) Pub Date : 2023-10-17 , DOI: 10.1007/s00592-023-02184-y
Xiang Li ₁ , Xiao Jiang ₁ , Mei Jiang ₁ , Zhi-Feng Wang ₁ , Tao Zhao ₁ , Si-Ming Cao ₁ , Qiu-Mei Li ₁

Affiliation

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.

中文翻译：

GLP-1RAs抑制NLRP3炎症小体信号通路的激活调节小鼠肾足细胞焦亡

客观的

足细胞作为肾小球的重要组成部分，与肾功能密切相关。足细胞的减少和损伤导致肾功能进一步下降，加重DKD的进展。胰高血糖素样肽1受体激动剂（GLP-1RAS）近年来在改善足细胞功能障碍方面引起了广泛关注，但具体机制仍不清楚。

方法

我们利用小鼠肾足细胞MPC5构建高糖损伤模型。 MTT法检测细胞活力； RT-qPCR、Western blotting检测NF-κB p65、NLRP3、GSDMD、N-GSDMD、caspase-1、cleaved-caspase-1的表达量,ELISA法检测炎症因子IL-1β的表达量和IL-18。