Pyroptosis in diabetic nephropathy

[Display omitted] •Pyroptosis is pro-inflammatory-programmed cell death.•Caspase-1/4/5/11-dependent inflammasome pathways mainly participate in pyroptosis.•Caspase-3/8 also induces pyroptosis.•NLRP3 inflammasome activation plays a critical role in the pathogenesis of DN.•Our article summarizes the mechanism of pyroptosis and its role in the pathogenesis of DN.•Our article suggests that some investigational compounds have promising therapeutic effects in treating and managing DN. Diabetic nephropathy (DN), a sterile inflammatory disease, is a serious complication of diabetes mellitus. However, recent evidence indicates that pyroptosis, a new term for pro-inflammatory cell death featured by gasdermin D (GSDMD)-stimulated plasma membrane pore generation, cell expansion and rapid lysis with the extensive secretion of pro-inflammatory factors, including interleukin-1β (IL-1β) and −18 (IL-18) may be involved in DN. Caspase-1-induced canonical and caspase-4/5/11-induced non-canonical inflammasome-signaling pathways are mainly believed to participate in pyroptosis-mediated cell death. Further research has uncovered that activation of the caspase-3/8 signaling pathway may also activate pyroptosis. Accumulating evidence has shown that NLRP3 inflammasome activation plays a critical role in promoting the pathogenesis of DN. In addition, current studies have suggested that pyroptosis-induced cell death promotes several diabetic complications that include DN. Our present study briefs the cellular mechanisms of pyroptosis-related signaling pathways and their impact on the promotion of DN. In this review, several investigational compounds suppressing pyroptosis-mediated cell death are explored as promising therapeutics in DN.