A novel redox signalling axis mediates nicotine-induced podocyte injury
Nicotine has been shown to induce Nlrp3 inflammasome activation, thereby contributing to podocyte injury. The molecular mechanisms underlying this process remain largely unknown. The present study investigated the role o
This study examined the molecular mechanisms underlying nicotine-induced podocyte injury. Researchers investigated the role of membrane raft-associated redox signalling in nicotine-induced Nlrp3 inflammasome activation and podocyte dysfunction. The findings demonstrate that membrane raft-associated redox signalling plays a critical role in driving nicotine-induced NLRP3 inflammasome activation and podocyte injury. The NADPH oxidase subunits gp91phox and p47phox were recruited and aggregated within membrane raft clusters, leading to the formation of a membrane raft redox signalling platform. This platform was inhibited by pretreatment with the membrane raft disruptor methyl-β-cyclodextrin or the NADPH oxidase inhibitor diphenyleneiodonium. The study also showed that nicotine markedly enhanced the colocalization of Nlrp3 with ASC and caspase-1, indicating inflammasome assembly, and significantly increased caspase-1 activity and IL-1β production. Furthermore, the study found that pretreatment with the caspase-1 inhibitor WEHD or the acid sphingomyelinase inhibitor amitriptyline largely preserved podocin expression. Overall, the results highlight the importance of membrane raft-associated redox signalling in the development of podocyte injury in response to nicotine exposure. The findings have implications for understanding the molecular mechanisms underlying nicotine-induced kidney damage and may contribute to the development of therapeutic strategies to mitigate this effect.