Canagliflozin Attenuates Podocyte Inflammatory Injury through Suppressing the TXNIP/NLRP3 Signaling Pathway in Diabetic Kidney Disease Mice

作者：Siyu Li, Jie Wang, Ying Chen, Yanlu Cheng, Yanan Wang, Nuowen Xu, Hao Wang, Li Wang, Yang-Feng Chi, Xiaoxue Ye, Yanting Shi, Ji Fang, Xingmei Yao, Jiebo Huang, Qing Xia, Tianli Bai, Bingbing Zhu · 发表于：Inflammation · 年份：2025 · DOI：10.1007/s10753-025-02258-9 · 被引用次数：10 · 研究领域：Diabetes Treatment and Management、Pancreatic function and diabetes、Renal Diseases and Glomerulopathies

Diabetic kidney disease (DKD), a leading cause of end-stage renal disease (ESRD), poses a serious threat to global health. Aseptic inflammation and pyroptosis of podocytes are crucial factors contributing to the pathogenesis and progression of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a novel class of antidiabetic agents widely used in clinical settings, may exert a protective effect on podocyte injury, although the underlying mechanisms remain poorly understood. This study uses the streptozotocin (STZ) -induced DKD mouse model to further explore the mechanism by which SGLT2i protect podocytes. The results demonstrated that Canagliflozin (CANA) treatment significantly improved serum creatinine levels, 24-h urinary albumin excretion, and urinary albumin-to-creatinine ratio (UACR) in DKD mice. Additionally, CANA treatment attenuated glomerular and podocyte injury, reducing overall pathological damage. Mechanistically, CANA reduced the expression of key inflammatory markers in the renal cortex of DKD mice, including TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, and GSDMD. These findings suggest that CANA may be an effective therapeutic agent for DKD by inhibiting the TXNIP-NLRP3 inflammasome pathway and preventing podocyte pyroptosis.