{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:55:53Z","timestamp":1787756153353,"version":"build-2784847793"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoxia is a prevalent pathological process in chronic rhinosinusitis with nasal polyps (CRSwNP), leading to a cascade of pathological events, including epithelial\u2010mesenchymal transition (EMT). However, the mechanisms underlying hypoxia\u2010induced EMT remain unclear. This study aims to elucidate the mechanisms driving EMT under hypoxic conditions in CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transcriptome and proteome analyses of hypoxia\u2010treated human nasal epithelial cells (HNECs) were performed to identify key molecules and pathways. The expression of hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1), pyruvate dehydrogenase kinase (PDK1), lactate dehydrogenase A (LDHA), and EMT markers was assessed in nasal tissues from CRSwNP patients. In vitro, cultured HNECs were exposed to hypoxia and lactate, or overexpressed PDK1, to evaluate changes in EMT markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypoxia activated the glycolysis\u2010related pathway in HNECs, with PDK1 and LDHA identified as significantly upregulated glycolysis\u2010related enzymes. The expression of PDK1 and LDHA was closely correlated with HIF\u20101\u03b1 and EMT markers in nasal tissues. Hypoxia induced an increase in PDK1 and LDHA expression, lactate production, and EMT occurrence in HNECs. PDK1 overexpression or lactate stimulation also triggered EMT, while PDK1 inhibition attenuated hypoxia\u2010induced EMT in HNECs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study is the first to reveal that hypoxia\u2010induced activation of PDK1 plays a critical role in regulating EMT by promoting lactate production, thereby providing a potential therapeutic target for CRSwNP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clt2.70048","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T16:47:45Z","timestamp":1743785265000},"source":"Crossref","is-referenced-by-count":2,"title":["Targeting PDK1: A novel approach to combat hypoxia\u2010induced epithelial\u2010mesenchymal transition in chronic rhinosinusitis with nasal polyps"],"prefix":"10.1002","volume":"15","author":[{"given":"Sicen","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Laboratory of Allergic Diseases Beijing Municipal Education Commission Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Beijing Institute of Otolaryngology Ministry of Education Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyan","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Laboratory of Allergic Diseases Beijing Municipal Education Commission Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Beijing Institute of Otolaryngology Ministry of Education Capital Medical University  Beijing 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