{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:30:25Z","timestamp":1779118225525,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Kawasaki disease (KD) is a medium-vessel vasculitis predominantly affecting children under 5 years of age and may involve the coronary arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mouse KD model was induced by <jats:italic>Candida albicans<\/jats:italic> cell wall extracts (CAWS), cardiac tissues were analyzed through integrated lactylomic and proteomic profiling. The lysine lactylation (Kla) results were normalized to the proteomic data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elevated serum lactate and lactate dehydrogenase (LDH) levels were observed in KD patients. Given lactate\u2019s role as a substrate for Kla, this study investigated Kla modifications in KD. Proteomic analysis identified 150 upregulated proteins and 18 downregulated proteins, with 38.1% located in the cytoplasm and significant enrichment in immune-related pathways. After normalization, 41 sites in 37 proteins were found to be upregulated in the Kla data, with no downregulated sites. Approximately 67.57% of the altered proteins were localized in the mitochondria. Bioinformatics analysis indicated alterations in aerobic respiration, energy production and conversion, and key immune- and metabolism-related pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study enhances the understanding of Kla modifications in the development of KD and may inform targeted therapies for its prevention and improved prognosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1550220","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:52:12Z","timestamp":1741243932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenyu","family":"Zhuo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajia","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41419-023-06272-3","article-title":"Inhibition of PDGFR\u03b2 alleviates endothelial cell apoptotic injury caused by DRP-1 overexpression and mitochondria fusion failure after mitophagy","volume":"14","author":"An","year":"2023","journal-title":"Cell Death Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"112957","DOI":"10.1016\/j.intimp.2024.112957","article-title":"The role of PI3K-Akt-mTOR axis in Warburg effect and its modification by specific protein kinase inhibitors in human and rat inflammatory macrophages","volume":"141","author":"B\u00f6gel","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0140-6736(04)16814-1","article-title":"Kawasaki syndrome","volume":"364","author":"Burns","year":"2004","journal-title":"Lancet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"123810","DOI":"10.1016\/j.ijbiomac.2023.123810","article-title":"Lactate induces tumor-associated macrophage polarization independent of mitochondrial pyruvate carrier-mediated metabolism","volume":"237","author":"Fang","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"107228","DOI":"10.1016\/j.phrs.2024.107228","article-title":"PGC-1\u03b1 loss promotes mitochondrial protein lactylation in acetaminophen-induced liver injury via the LDHB-lactate axis","volume":"205","author":"Hong","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41392-024-01954-6","article-title":"Metabolic regulation of the immune system in health and diseases: mechanisms and interventions","volume":"9","author":"Hu","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1542\/peds.54.3.271","article-title":"A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan","volume":"54","author":"Kawasaki","year":"1974","journal-title":"Pediatrics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"43732","DOI":"10.1038\/srep43732","article-title":"Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis","volume":"7","author":"Kimura","year":"2017","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/s44161-023-00314-x","article-title":"MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease","volume":"2","author":"Lin","year":"2023","journal-title":"Nat. Cardiovasc Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e927","DOI":"10.1161\/CIR.0000000000000484","article-title":"Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American heart association","volume":"135","author":"McCrindle","year":"2017","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1111\/chd.12498","article-title":"Kawasaki disease: state of the art","volume":"12","author":"Newburger","year":"2017","journal-title":"Congenit. Heart Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1542\/peds.2004-2182","article-title":"Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, council on cardiovascular disease in the young, American heart association","volume":"114","author":"Newburger","year":"2004","journal-title":"Pediatrics"},{"key":"B13","first-page":"S9","article-title":"Murine model of Kawasaki disease induced by mannoprotein-beta- glucan complex, CAWS, obtained from Candida albicans","volume":"57","author":"Ohno","year":"2004","journal-title":"Jpn. J. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"374","DOI":"10.3389\/fped.2018.00374","article-title":"The epidemiology and pathogenesis of Kawasaki disease","volume":"6","author":"Rowley","year":"2018","journal-title":"Front. Pediatr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1136\/archdischild-2014-307536","article-title":"The epidemiology of Kawasaki disease: a global update","volume":"100","author":"Singh","year":"2015","journal-title":"Arch. Dis. Child."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1084\/jem.20151853","article-title":"GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease","volume":"213","author":"Stock","year":"2016","journal-title":"J. Exp. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.micpath.2007.10.013","article-title":"The influence of culture conditions on vasculitis and anaphylactoid shock induced by fungal pathogen Candida albicans cell wall extract in mice","volume":"44","author":"Tada","year":"2008","journal-title":"Microb. Pathog."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6210","DOI":"10.7150\/ijbs.75434","article-title":"Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages","volume":"18","author":"Wang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s13059-023-02931-y","article-title":"YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2","volume":"24","author":"Wang","year":"2023","journal-title":"Genome Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5444","DOI":"10.1038\/s41467-021-25771-5","article-title":"Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2384889","DOI":"10.1080\/08916934.2024.10.1080\/08916934.2024.23848894889","article-title":"LDHA-induced histone lactylation mediates the development of osteoarthritis through regulating the transcription activity of TPI1 gene","volume":"57","author":"Xia","year":"2024","journal-title":"Autoimmunity"},{"key":"B22","doi-asserted-by":"publisher","first-page":"116952","DOI":"10.1016\/j.ecoenv.2024.116952","article-title":"Glycolytic reprogramming governs crystalline silica-induced pyroptosis and inflammation through promoting lactylation modification","volume":"283","author":"You","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e2451018","DOI":"10.1002\/eji.202451018","article-title":"Regulation of IFN-\u03b3 production by ZFP36L2 in T cells is time-dependent","volume":"54","author":"Zandhuis","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41422-023-00844-w","article-title":"\u03b1-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure","volume":"33","author":"Zhang","year":"2023","journal-title":"Cell Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"155957","DOI":"10.1016\/j.metabol.2024.155957","article-title":"Lactate and lactylation in cardiovascular diseases: current progress and future perspectives","volume":"158","author":"Zhu","year":"2024","journal-title":"Metabolism"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1550220\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:52:15Z","timestamp":1741243935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1550220\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":26,"alternative-id":["10.3389\/fcell.2025.1550220"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1550220","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]},"article-number":"1550220"}}