PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition - PubMed
5 hours ago
- #epigenetics
- #asthma
- #metabolism
- Asthmatic airways show lactate-driven glutaminolysis leading to lactate and succinate accumulation.
- PCK2 succinylation at K100 enhances its stability by antagonizing ubiquitination, creating a lactate-generating feedback loop.
- Accumulated lactate triggers PQBP1 lactylation at K223, which inhibits the PRMT5/WDR77 complex.
- This inhibition erases H4R3me2s repressive marks from proinflammatory gene promoters, causing transcriptional derepression.
- Airway epithelium-specific Pqbp1 knockout reduces inflammation, goblet cell hyperplasia, and Th2 responses.
- Pck2-shRNA or oxamate treatment ameliorates asthmatic pathology.
- The study identifies a PCK2-lactate-PQBP1-PRMT5 axis linking metabolic reprogramming to epigenetic dysregulation in asthma.