Abstract
BACKGROUND: Inflammation and oxidative stress are important pathological processes of contrast-induced acute renal injury (CIAKI). This study explored whether DMF had therapeutic effects and investigated the underlying mechanism in CIAKI. METHODS: A CIAKI animal model was established in C57BL/6J mice with iohexol, and DMF was used as an intervention. In vitro, HK-2 cells were treated with iohexol and DMF. RNA-seq analysis was performed on the renal tissue of the mice. Protein-protein interaction (PPI), and enrichment analysis were subsequently conducted. In addition, endoplasmic reticulum stress (ERS) activation and STAT3 inhibition were used to study the relationships among ERS, the JAK2-STAT3 pathway and pyroptosis. RESULTS: DMF improved the renal function of CIAKI model mice. Enrichment analysis revealed that the differentially expressed genes (DEGs) were enriched mostly in the acute phase response and the JAK-STAT pathway. The results revealed that inflammation, ERS and pyroptosis increased in the CIAKI group but decreased after DMF treatment. Further study revealed that the JAK2-STAT3 pathway was overactivated in vivo and in vitro and that DMF inhibited the JAK2-STAT3 pathway. In addition, ERS activation could increase the JAK2-STAT3 pathway and pyroptosis, while STAT3 knockdown could reverse pyroptosis, indicating that ERS could activate the JAK2-STAT3 pathway, further triggering pyroptosis. DMF ameliorated pyroptosis through regulating ERS and the JAK2-STAT3 pathway in CIAKI. CONCLUSION: This study demonstrated that DMF had renoprotective effects on CIAKI. DMF ameliorated pyroptosis through the inhibition of ERS and the JAK2-STAT3 pathway.