{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:21:53Z","timestamp":1784233313662,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ50739"],"award-info":[{"award-number":["2025JJ50739"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute lung injury (ALI) is characterized by significant neutrophil infiltration in the lungs, representing a life\u2010threatening condition with diverse etiologies. However, the mechanisms regulating neutrophil\u2013alveolar epithelial interactions and the pathophysiological roles of neutrophil infiltration in ALI remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A dose of 20\u2009mg\/kg lipopolysaccharide (LPS) was intratracheally instilled to induce ALI models in 10\u2010week\u2010old male microRNA\u2010223 knockout mice (miR\u2010223\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) and wild\u2010type (WT) mice, with control group mice receiving an equal volume of phosphate\u2010buffered saline (PBS). After 24\u2009h of instillation, lung tissues and peripheral blood were collected from the mice. In vivo, quantitative PCR (qPCR) measured miR\u2010223 and neutrophil elastase (NE) mRNA levels, while Western blot (WB), enzyme\u2010linked immunosorbent assay (ELISA), and hematoxylin\u2013eosin (H&amp;E) staining assessed neutrophil extracellular traps (NETs) markers (H3Cit, myeloperoxidase [MPO]), inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106), and lung injury severity. In vitro, HL\u201060\u2010derived neutrophil\u2010like cells were cocultured with alveolar epithelial cells under LPS stimulation. The roles of the miR\u2010223\/NE\/NETs axis were further investigated using the NETs inhibitor GSK484 and the NE inhibitor Sivelestat.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WB experiments showed an increase in NETs\u2010related proteins MPO and H3Cit in the lungs of WT ALI mice, with significantly enhanced expression in miR\u2010223\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. The lung injury scores and mortality rates in miR\u2010223\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were significantly exacerbated, accompanied by increased neutrophil infiltration in the lungs. Levels of inflammatory factors (TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106) in the serum of miR\u2010223\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were significantly elevated. In vitro coculture experiments demonstrated that miR\u2010223 deficiency in neutrophil\u2010like cells augmented NETs formation and inflammatory responses, leading to increased damage to alveolar epithelial cells. However, in vivo inhibition of NETs with GSK484 or NE with Sivelestat in miR\u2010223\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice significantly attenuated neutrophil infiltration, inflammation, and lung injury, and improved survival. Similarly, Sivelestat pretreatment reduced NET formation and conferred protection against ALI. Consistent with the in vivo findings, inhibition of NETs with GSK484 or NE with Sivelestat in the coculture system similarly attenuated epithelial damage and inflammatory response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals that the miR\u2010223\/NE axis critically regulates NETs formation, modulating neutrophil inflammatory infiltration and neutrophil\u2013epithelial interactions to exacerbate ALI. These findings provide potential therapeutic targets for ALI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/1621608","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T12:23:01Z","timestamp":1768220581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MicroRNA\u2010223\/NE Signaling Pathway Inhibits Lipopolysaccharide\u2010Induced Acute Lung Injury by Regulating Neutrophil Extracellular Traps"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5172-2508","authenticated-orcid":false,"given":"Zhengpeng","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0837-4643","authenticated-orcid":false,"given":"Yuexiang","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2746-6308","authenticated-orcid":false,"given":"Xue","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0443-586X","authenticated-orcid":false,"given":"Zhaoxia","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202303-0558WS"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00157-0"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01485-4"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0291"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30188-1"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202250010"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1331000"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.953195"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031464"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1012539"},{"key":"e_1_2_8_11_2","article-title":"Thomas Preiss, mRNA Isoform Diversity Can Obscure Detection of miRNA-Mediated Control of Translation","volume":"17","author":"Jennifer L.","year":"2011","journal-title":"RNA"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07242"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06607"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05121.x"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.005"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-7"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.43108"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27428-9"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3NR03120A"},{"key":"e_1_2_8_20_2","doi-asserted-by":"crossref","unstructured":"BenderR. G. SirotaS. B. andSwetschinskiL. R. et al.Global Regional and National Incidence and Mortality Burden of Non-COVID-19 Lower Respiratory Infections and Aetiologies 1990\u20132021: A Systematic Analysis From the Global Burden of Disease Study 2021 2024 24 no. 9 974\u20131002 https:\/\/doi.org\/10.1016\/S1473-3099(24)00176-2.","DOI":"10.1016\/S1473-3099(24)00176-2"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00311.2013"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160462"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10396"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.05.012"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12099"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201516"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-016-0449-x"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-990OC"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.145"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c08926"},{"key":"e_1_2_8_32_2","doi-asserted-by":"crossref","unstructured":"ChenY. MaoR. ChangQ. YuanY. ZhangH. andLiF. A Causal Effects of Neutrophil Extracellular Traps and Its Biomarkers on Acute Respiratory Distress Syndrome: A Two-Sample Mendelian Randomization study.Scientific Reports 2025 15 no. 1 https:\/\/doi.org\/10.1038\/s41598-025-95676-6 11995.","DOI":"10.1038\/s41598-025-95676-6"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.04.023"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1170"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073787"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1432018"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/1621608","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/mi\/1621608","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/1621608","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T12:23:05Z","timestamp":1768220585000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/mi\/1621608"}},"subtitle":[],"editor":[{"given":"Duo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/mi\/1621608"],"URL":"https:\/\/doi.org\/10.1155\/mi\/1621608","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1621608"}}