OBJECTIVE: To investigate the effects and underlying mechanism of gasdermin D on pyroptosis in sepsis-induced acute kidney injury. STUDY DESIGN: C57BLk/6J mice received lipopolysaccharide (LPS) (40 mg/kg body weight, i.p.) or an equal volume of 0.9% saline as a control. Histological analysis was performed by staining with HE assay. The concentration of serum creatinine, IL-1β, and IL-18 were analyzed using commercial kits. RTEC cells were transfected with Plin5 plasmid, siPlin5 plasmid, NLRP3 plasmid, or negative mimics using Lipofectamine 2000. PC12 cells were induced with 100 ng/mL LPS for 4 hours and then cultured with ATP (1 nM) for 1 hour after transfection at 48 hours. Apoptosis rate was determined by flow cytometry. The protein expression levels of gasdermin D, NLRP3, and GAPDH were detected by western blot. RESULTS: Our study demonstrated that the expression of gasdermin D was upregulated in mice with sepsis-induced acute kidney injury. Overexpression of gasdermin D promoted inflammation and pyroptosis in vitro, while downregulation of gasdermin D decreased inflammation and pyroptosis in vitro. NLRP3 inflammasome is an important target of gasdermin D on inflammation in sepsis-induced acute kidney injury. The inhibition of NLRP3 attenuated the effects of gasdermin D on inflammation in sepsis-induced acute kidney injury. CONCLUSION: Collectively, this study suggested that gasdermin D regulated sepsis-induced acute kidney injury via promotion of pyroptosis by activating NLRP3 inflammasome. © Science Printers and Publishers, Inc.