Metformin Corrects Glucose Metabolism Reprogramming and NLRP3 Inflammasome-Induced Pyroptosis via Inhibiting the TLR4/NF-κB/PFKFB3 Signaling in Trophoblasts: Implication for a Potential Therapy of Preeclampsia

Figure 8

A mechanism diagram. LPS-induced TLR4/NF-κB activation caused NLRP3 inflammasome-induced pyroptosis in trophoblasts. Besides, the TLR4/NF-κB signaling caused mitochondrial destruction and dysfunction; meanwhile, it reprogrammed the glycometabolism to glycolysis with increased PFKFB3 expression. The TLR4/NF-κB signaling induced PFKFB3 expression by transcriptional factor NF-κB1 binding PFKFB3 promoter region. Glycolytic enzyme PFKFB3 further exacerbated NLRP3 inflammasome-induced pyroptosis, leading to positive feedback. Metformin inhibited the TLR4/NF-κB/PFKFB3 signaling to break the vicious circle, expected to be a novel candidate for preeclamptic therapies.