{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:35:32Z","timestamp":1783042532497,"version":"3.54.6"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2024206398"],"award-info":[{"award-number":["H2024206398"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170018"],"award-info":[{"award-number":["82170018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lactate, traditionally viewed as a glycolysis byproduct, has emerged as an important mediator influencing immunity, inflammation, and tissue damage. While PM2.5 exposure is known to cause various metabolic disturbances, the role of lactate metabolism in PM2.5\u2010induced lung injury remains unclear. This study aims to elucidate the mechanisms underlying PM2.5\u2010induced lung injury from a metabolic perspective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lactate and pyruvate assays were performed to assess metabolic changes following PM2.5 exposure. Protein expression and tissue damage were assessed using Western blot, IHC, ELISA, and TUNEL staining. The biological role of USP38 in PM2.5\u2010induced injury was identified using gain\u2010 and loss\u2010of\u2010function experiments. Co\u2010immunoprecipitation and ubiquitination assays were conducted to analyze the interaction between USP38 and MCT1, as well as the regulation of MCT1 deubiquitination. The role of MCT1 in lactate metabolism and PM2.5\u2010induced apoptosis was validated through gene editing. Proteomics revealed the potential mechanisms involved in USP38 regulation of apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrated that PM2.5 exposure induced lactate accumulation, leading to cell apoptosis and lung injury. USP38 stabilized MCT1 expression by deubiquitination, facilitating lactate export and reducing apoptosis and lung injury caused by lactate accumulation. Mechanistically, PM2.5 increased lactate production, suppressed AKT\/mTOR pathway activation, and promoted apoptosis and lung injury. USP38 promoted lactate export through MCT1, activated the AKT\/mTOR pathway, and mitigated PM2.5\u2010induced lung injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>USP38 reduces lactate accumulation by promoting AKT\/mTOR pathway activation through MCT1\u2010mediated lactate export, thereby alleviating PM2.5\u2010induced lung injury. These findings reveal a novel mechanism of PM2.5\u2010related lung injury and highlight potential therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.70028","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T11:00:23Z","timestamp":1744023623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of Lactate Accumulation via USP38\u2010Mediated MCT1 Deubiquitination Activates AKT\/mTOR Signaling to Mitigate PM2.5\u2010Induced Lung Injury"],"prefix":"10.1002","volume":"39","author":[{"given":"Zixiao","family":"Chen","sequence":"first","affiliation":[{"name":"The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases  Shijiazhuang Hebei Province 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