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This study aimed to investigate the role and regulatory mechanism of KCNQ1 overlapping transcript 1 (KCNQ1OT1) in OLV\u2010induced lung injury and LPS\u2010induced type II alveolar epithelial cell (AECII) apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The rat OLV model was established, and the effects of KCNQ1OT1 on OLV\u2010induced ALI in vivo were explored. Bax and Caspase\u20103 expression in rat lung tissues was measured by immunochemistry (IHC). AECIIs were isolated from rat lungs and treated with LPS or normal saline (control) for in vitro analysis. The expression of KCNQ1OT1, miR\u2010129\u20105p, and HMGB1 was measured by quantitative real\u2010time PCR (qRT\u2010PCR) or Western blot (WB). Cell proliferation and apoptosis were examined by 3\u2010(4,5)\u2010dimethylthiahiazo (\u2010z\u2010y1)\u20103,5\u2010di\u2010 phenytetrazoliumromide (MTT) and flow cytometry. The downstream targets of KCNQ1OT1 were predicted by bioinformatics, and the binding relationship between KCNQ1OT1 and miR\u2010129\u20103p was verified by dual\u2010luciferase reporter assays. The potential target of miR\u2010129\u20105p was further explored on the Targetscan website and revealed to target HMGB1. Enzyme\u2010linked immunosorbent assay (ELISA) or WB was adopted to determine the levels of IL\u20101\u03b2, TNF\u2010\u03b1, MDA, SOD, heparanase (HPA), matrix metalloproteinase 9 (MMP9), heparan sulfate (HS) and syndecan\u20101 (SDC\u20101).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>KCNQ1OT1 and HMGB1 were up\u2010regulated during OLV\u2010induced lung injury, and their expression was positively correlated. KCNQ1OT1 knockdown reduced OLV\u2010induced pulmonary edema and lung epithelial cell apoptosis, increased vascular permeability, reduced IL\u20101\u03b2, TNF\u2010\u03b1, MDA, and SOD levels and glycocalyx markers by targeting miR\u2010129\u20105p or upregulating HMGB1. Overexpressing KCNQ1OT1 promoted cell apoptosis, reduced cell proliferation, aggravated inflammation and oxidative stress, and up\u2010regulated HMGB1, HPA and MMP9 in LPS\u2010treated AECIIs, while the HMGB1 silencing showed the opposite effects. MiR\u2010129\u20105p mimics partially eliminated the KCNQ1OT1\u2010induced effects, while recombinant HMGB1 restored the effects of miR\u2010129\u20105p overexpression on AECIIs. Additionally, KCNQ1OT1 was demonstrated to promote the activation of the p38 MAPK\/Akt\/ERK signaling pathways in AECIIs via HMGB1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>KCNQ1OT1 knockdown alleviated AECII apoptosis and EG damage during OLV by targeting miR\u2010129\u20105p\/HMGB1 to inactivate the p38 MAPK\/Akt\/ERK signaling. The findings of our study might deepen our understanding of the molecular basis in OLV\u2010induced lung injury and provide clues for the targeted disease management.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tox.24201","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T06:25:38Z","timestamp":1710570338000},"page":"3578-3596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Down\u2010regulating <scp>lncRNA KCNQ1OT1<\/scp> relieves type <scp>II<\/scp> alveolar epithelial cell apoptosis during one\u2010lung ventilation via modulating <scp>miR<\/scp>\u2010129\u20105p\/<scp>HMGB1<\/scp> axis induced pulmonary endothelial glycocalyx"],"prefix":"10.1002","volume":"39","author":[{"given":"Zhenghuan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Affiliated Cancer Hospital of Nanjing Medical University  Nanjing City 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