PGK1 Lactylation-Driven Self-Reinforcing Loop Orchestrates Glycolytic Reprogramming in FSP1+ Macrophages in Liver Fibrosis - PubMed
4 hours ago
- #Liver Fibrosis
- #Glycolysis
- #Macrophages
- Liver fibrosis treatment is limited, with unclear roles of lactate-mediated lactylation in the hepatic microenvironment.
- A pathogenic FSP1+ macrophage subset was identified as a key therapeutic target in liver fibrosis.
- FSP1 interacts with PKM2 in macrophages, enhancing glycolysis and lactate production, promoting PGK1 lactylation.
- PGK1 lactylation at K353 creates a positive feedback loop, amplifying glycolysis and blocking mitochondrial pyruvate metabolism.
- A cell-penetrating peptide targeting PGK1-K353 lactylation was developed, showing promise in attenuating liver fibrosis progression.
- The study reveals the FSP1-glycolysis-lactylation axis as critical in fibrotic metabolism and suggests new therapeutic strategies.