Methylation of TTC4 interaction with HSP70 inhibits pyroptosis in macrophages of sepsis-induced lung injury by NLRP3 inflammation.

Acute lung injury (ALI) is an acute infectious diseases caused by a variety of factors. The function of TTC4 in sepsis-induced lung injury remains largely unknown. This study aimed to explore the critical role of TTC4 in sepsis-induced lung injury. Mice anaesthetized using pentobarbital sodium and subjected to cecal ligation and puncture (CLP) surgery. TTC4 expression levels in patients with sepsis-induced lung injury were down-regulated. The inhibition of TTC4 gene promoted lung injury in mice model of sepsis. TTC4 gene improved inflammation in vitro model and mice model. TTC4 gene reduced pyroptosis in macrophages of sepsis-induced lung injury by the inhibition of mitochondrial damage. TTC4 gene induced HSP70 expression to reduce NLRP3-induced pyroptosis in macrophages. TTC4 protein interlinked HSP70 protein. The activation of HSP70 reduced the effects of sh-TTC4 in model of sepsis-induced lung injury through mitochondrial damage. m6A-forming enzyme METTL3 reduced TTC4 stability. Our study suggests the m6A forming enzyme METTL3 control TTC4 reduced inflammation and pyroptosis in model of sepsis-induced lung injury through inhibition of mitochondrial damage by HSP70/ROS/NLRP3 signaling pathway, TTC4 gene as an represents a potential therapeutic strategy for the treatment of sepsis-induced lung injury.