FIGURE 5.

HIF-1α/NLRP3 signaling pathway is involved in the regulation of pyroptosis. (1) HIF-1α can be degraded in normoxia. (2) In hypoxia, NF-κB and PI3K/Akt/mTOR/NF-κB signaling pathway can be activated, and caspase-8 can also promote the nuclear translocation of NF-κB. (3) NF-κB directly bound to the HIF-1α promoter and enhanced its transcription. HIF-1α could modulate the activation of the NLRP3 inflammasome, and the increase in VEGF-A can also result in NLRP3 inflammasome activation. (4) HIF-2α binds directly to the Cpt1a promoter and inhibits the expression of it. HIF-2α can also regulate the H3K27me3 methylation during NLRP3 inflammasome activation. (5) Both Cpt1a and miR-129/IGF-1/PI3K/Akt/GSK3β signaling pathway can regulate the expression of ASC which is involved in the activation of NLRP3 inflammasome.