CircEXOC5 facilitates cell pyroptosis via epigenetic suppression of Nrf2 in septic acute lung injury.

Acute lung injury (ALI) caused by sepsis is characterized by a destructive high inflammatory response in lungs, which is the ultimate cause of high mortality to patients diagnosed with sepsis. The objective of the present study is to explore the effect and related mechanisms of circEXOC5 on pyroptosis in septic ALI. Sepsis ALI mouse model was induced and established by CLP induction and sepsis MPVEC cell model by LPS. HE staining was used to detect lung tissue pathological changes. ELISA, flow cytometry, and Western blot were utilized to evaluate the release of inflammatory cytokines and cell pyroptosis, and RIP was applied to verify the binding relationship between EZH2 and circEXOC5 or Nrf2. Finally, the interaction between CircEXOC5 and EZH2, H3k27me3, and Nrf2 promoter regions was clarified using ChIP. CircEXOC5 levels were notably ascended in the lung tissues of septic ALI mice. And silencing circEXOC5 inhibited cell pyroptosis and the release of inflammatory cytokines in MPVEC stimulated by LPS. In addition, RIP and ChIP indicated that Nrf2 expression in MPVECs cells could be inhibited by circEXOC5 via recruiting EZH2. In addition, ML385 (a specific inhibitor of Nrf2) reversed the efficacy of Knockdown of circEXOC5 on the Inhibition of pyroptosis and inflammation of MPVEC cells stimulated by LPS. These results indicated that CircEXOC5 could promote cell pyroptosis through epigenetic inhibition of Nrf2 in septic ALI.