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Phosphoenolpyruvate carboxykinase 2 (PCK2) succinylation at K100 enhanced stability by antagonizing ubiquitination, creating a lactate-generating feedback loop. Accumulated lactate triggered polyglutamine-binding protein 1 (PQBP1) lactylation at K223, enabling protein arginine methyltransferase 5 (PRMT5)\/WD repeat domain 77 complex inhibition. This erased H4R3me2s repressive marks from proinflammatory gene promoters, particularly mitogen-activated protein kinase pathway genes, causing transcriptional derepression. Airway epithelium-specific\n                    <jats:italic toggle=\"yes\">Pqbp1<\/jats:italic>\n                    knockout reduced inflammation, goblet cell hyperplasia, and T helper 2 responses.\n                    <jats:italic toggle=\"yes\">Pck2<\/jats:italic>\n                    -short hairpin RNA or oxamate treatment ameliorated asthmatic pathology.\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    We identified a PCK2\u2013lactate\u2013PQBP1\u2013PRMT5 axis linking metabolic reprogramming to epigenetic dysregulation in asthma. PCK2-K100 succinylation drives lactate accumulation, inducing PQBP1-K223 lactylation that inhibits PRMT5 and activates inflammatory genes, representing a therapeutic target for asthma.\n                  <\/jats:p>","DOI":"10.34133\/research.1321","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:19:21Z","timestamp":1779427161000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":2,"title":["PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition"],"prefix":"10.34133","volume":"9","author":[{"given":"Qiaoyun","family":"Bai","sequence":"first","affiliation":[{"name":"Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, \rYanbian University, Yanji 133002, P.R. China."},{"name":"Department of Anatomy, Histology and Embryology, \rYanbian University Medical College, Yanji 133002, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningpo","family":"Ding","sequence":"additional","affiliation":[{"name":"Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, \rYanbian University, Yanji 133002, P.R. China."},{"name":"Department of Anatomy, Histology and Embryology, \rYanbian University Medical College, Yanji 133002, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rixin","family":"Feng","sequence":"additional","affiliation":[{"name":"Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, \rYanbian University, Yanji 133002, P.R. China."},{"name":"Department of Anatomy, Histology and Embryology, \rYanbian University Medical College, Yanji 133002, P.R. 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