Pyroptosis in diabetic nephropathy

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.