{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:40:24Z","timestamp":1786725624546,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Exposure of the lungs to high O2 levels, can lead to a noninfectious lung damage known as hyperoxia\u2010induced lung injury (HILI). Melatonin stimulation can enhance the efficacy of stem cells in some diseases. This study aims to investigate the mechanism of exosomes secreted by mesenchymal stem cells (MSCs) stimulated by melatonin in HILI. The MSCs\u2010derived exosomes were isolated and identified after stimulation with melatonin, and the neonatal rat model of HILI was constructed. After injection of exosomes and related lentiviruses, the ratio of wet lung to dry lung was calculated to evaluate pulmonary edema. Inflammatory factors in medium or serum were measured by ELISA. HE staining was used to evaluate the pathological status of lung tissue. Masson staining was used to evaluate collagen deposition in lung tissue. Lung cell apoptosis was detected by Tunel staining. In vitro model of HILI was established, CCK\u20108 and EDU staining were used to detect cell viability and proliferation, and flow cytometry was used to detect cell apoptosis. The binding relationship between LINC00052, miR\u2010152\u20103p, and KLF4 was verified through bioinformatics websites, dual luciferase reporter experiments, RIP experiments, and RNA pull down experiments. Melatonin\u2010stimulated MSCs\u2010derived exosomes could alleviate HILI. Exosomes had a therapeutic effect on HILI neonatal rats by carrying LINC00052. Inhibition of LINC00052 reversed the therapeutic effect of exosomes on HILI, while low expression of miR\u2010152\u20103p or inducing KLF4 negated the effect of sh\u2010LINC00052. LINC00052 bound to miR\u2010152\u20103p. miR\u2010152\u20103p targeted KLF4. In vitro, melatonin\u2010stimulated MSC\u2010derived exosomes alleviated the cytotoxicity and cell viability inhibition of AEC\u2010II cells induced by hyperoxia. KLF4 overexpression activated NRF2 signaling in AEC\u2010II cells. LINC00052 in MSCs\u2010derived exosomes stimulated by melatonin activates the Nrf2 pathway through the miR\u2010152\u20103p\/KLF4 axis to alleviate HILI, which may be a potential therapeutic approach for HILI.<\/jats:p>","DOI":"10.1002\/jbt.70241","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T15:05:21Z","timestamp":1745247921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Melatonin\u2010Stimulated Mesenchymal Stem Cells\u2010Derived Exosomes Carrying LINC00052 Alleviate Hyperoxic Lung Injury by Promoting miR\u2010152\u20103p\u2010KLF4\u2010Nrf2 Pathway"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9012-3898","authenticated-orcid":false,"given":"Nan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine General Hospital of Northern Theater Command Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeYu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Information Engineering Liaoning University of Traditional Chinese Medicine Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine General Hospital of Northern Theater Command Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Liaoning University of Traditional Chinese Medicine Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine General Hospital of Northern Theater Command Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine General Hospital of Northern Theater Command Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HongXu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine General Hospital of Northern Theater Command Shenyang City Liaoning Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra067279"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2016.4141"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01349-y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-021-00374-4"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2741\/3179"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.02.061"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194815"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2013.50"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.237"},{"issue":"8","key":"e_1_2_11_11_1","first-page":"2628","article-title":"Human Mesenchymal Stem Cells Attenuate Hyperoxia\u2010Induced Lung Injury Through Inhibition of the Renin\u2010Angiotensin System in Newborn Rats","volume":"10","author":"Chen C. 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