{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T21:58:01Z","timestamp":1780351081873,"version":"3.54.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Macrophages function as key orchestrators in the pathogenesis of acute lung injury (ALI). The current study sets out to investigate the molecular mechanism of transforming growth factor-\u03b2 (TGF\u03b21) in the regulation of M1 alveolar macrophage polarization in ALI by modulating DNA methyltransferase 1 (DNMT1), along with the microRNA (miR)-124\/Pellino 1 (PELI1)\/interferon regulatory factor 5 (IRF5) axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, ALI mouse models were established, and the proportion of M1 and M2 macrophages in mouse lung tissues was detected using flow cytometry. The targeting relationship between miR-124 and PELI1 was verified with the help of a dual luciferase gene reporter assay. Following TGF\u03b21 knockdown, RT-qPCR and Western blot assay were performed to analyze the expression patterns of TGF\u03b21, DNMT1, miR-124, and PELI1 and M1\/M2 polarization markers in the lung tissues of ALI mice. Immunofluorescence was further employed to detect nuclear translocation of IRF5 in macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The polarization of M1 macrophages was found to be positively correlated with the severity of lung injury. TGF\u03b21, DNMT1, PELI1 were highly expressed, while miR-124 was down-regulated in ALI mice, and IRF5 was primarily distributed in the nucleus. TGF\u03b21 promoted the polarization of M1 alveolar macrophages by up-regulating DNMT1. Furthermore, DNMT1 down-regulated the expression of miR-124, which led to enhancement of M1 alveolar macrophage polarization. Meanwhile, over-expression of miR-124 inhibited the nuclear translocation of IRF5 and suppressed M1 alveolar macrophage polarization. On the other hand, over-expression of PELI1 reversed the above trends.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, our findings indicated that TGF\u03b21 can promote the expression of DNMT1, which down-regulates miR-124 to activate PELI1 and nuclear translocation of IRF5, thereby aggravating ALI in mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.693981","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T12:46:10Z","timestamp":1629809170000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Transforming Growth Factor-\u03b21 Promotes M1 Alveolar Macrophage Polarization in Acute Lung Injury by Up-Regulating DNMT1 to Mediate the microRNA-124\/PELI1\/IRF5 Axis"],"prefix":"10.3389","volume":"11","author":[{"given":"Yongqi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanmei","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2019ai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104736","article-title":"Acute Lung Injury: The Therapeutic Role of Rho Kinase Inhibitors","volume":"155","author":"Abedi","year":"2020","journal-title":"Pharmacol. 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