PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition.
Qiaoyun Bai1,2, Ningpo Ding1,2, Rixin Feng1,2
1Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, P.R. China.
Research (Washington, D.C.)
|June 22, 2026
Summary
Metabolic reprogramming in asthma involves a PCK2-lactate-PQBP1-PRMT5 axis. PCK2 succinylation drives lactate accumulation, leading to PQBP1 lactylation, PRMT5 inhibition, and inflammatory gene activation, offering a therapeutic target.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Asthma pathogenesis involves chronic inflammation and metabolic reprogramming.
- The role of metabolites in shaping asthma epigenetics via posttranslational modifications is not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which metabolites influence epigenetic modifications in asthma.
- To identify key molecular players in the metabolic-epigenetic crosstalk driving asthma pathology.
Main Methods:
- Multi-omics analyses (metabolomics, PTM-proteomics, ChIP-seq) in house dust mite (HDM)-induced asthmatic mouse models.
- Gene editing and adeno-associated virus interventions for functional validation.
- Biochemical assays to confirm protein modifications and interactions.
Main Results:
- Asthmatic airways exhibit lactate-driven glutaminolysis with accumulated lactate and succinate.
- Phosphoenolpyruvate carboxykinase 2 (PCK2) succinylation at K100 enhances stability, promoting lactate production.
- Lactate accumulation induces polyglutamine-binding protein 1 (PQBP1) lactylation at K223, inhibiting PRMT5 and removing repressive H4R3me2s marks from inflammatory gene promoters.
- Airway-specific Pqbp1 knockout and Pck2 inhibition ameliorated asthma symptoms.
Conclusions:
- A novel PCK2-lactate-PQBP1-PRMT5 signaling axis links metabolic reprogramming to epigenetic dysregulation in asthma.
- PCK2 succinylation and subsequent PQBP1 lactylation promote inflammatory gene activation, representing a potential therapeutic target for asthma.
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