{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:32:04Z","timestamp":1785025924527,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["1R01AA029690\u201001A1"],"award-info":[{"award-number":["1R01AA029690\u201001A1"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA025857"],"award-info":[{"award-number":["R01AA025857"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alcohol use disorders (AUD) increase susceptibility to lung diseases. Ethanol suppresses nuclear factor erythroid 2\u2010related factor 2 (Nrf2), impairing pulmonary antioxidant and immune defenses. We showed that HIV\u2010mediated Nrf2 suppression in the lung is driven by miR\u2010144. We hypothesized that ethanol similarly suppresses Nrf2 by inducing miR\u2010144 in the lung.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>miR\u2010144 expression was quantified in lungs from rats chronically fed an ethanol\u2010containing diet and in rat alveolar epithelial cells (AEC), alveolar macrophages (AMs), and lung fibroblasts (PLF) treated with ethanol. The levels of the AP\u20101 subunits c\u2010Fos and c\u2010Jun, both total and phosphorylated, were quantified by western immunoblotting in rat PLF. The link between ethanol\u2010induced AP\u20101 activation and miR\u2010144 expression on Nrf2 and Nrf2\u2010regulated antioxidants was then assessed using c\u2010Fos silencing RNA and AP\u20101 inhibitors. The impact of manipulating miR\u2010144 expression and\/or activity on the expression of Nrf2 and two key Nrf2\u2010dependent antioxidants in ethanol\u2010treated PLF was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>miR\u2010144 expression was increased in the lungs of chronic ethanol\u2010fed rats, and ethanol exposure increased miR\u2010144 expression in AEC and PLF, with a trend toward increased expression in AM. Ethanol induced both total and phosphorylated c\u2010Fos protein and total c\u2010Jun protein in PLF. Inhibiting AP\u20101 with c\u2010Fos silencing RNA or AP\u20101 inhibitors blocked ethanol\u2010induced miR\u2010144 expression in PLF. Furthermore, RNA silencing of c\u2010Fos or inhibiting miR\u2010144 restored the expression of Nrf2 and the Nrf2\u2010dependent antioxidants GCLC and NQO\u20101 in ethanol\u2010treated PLF. In contrast, direct overexpression of miR\u2010144 suppressed Nrf2, GCLC, and NQO\u20101, thereby reproducing the pathophysiological effects of ethanol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ethanol induces miR\u2010144 expression in the lung, mediated by AP\u20101 activation. These steps can be implicated in the ethanol\u2010mediated inhibition of Nrf2 and the downstream suppression of Nrf2\u2010dependent antioxidant and immune defenses. These results suggest that miR\u2010144 could be a novel therapeutic target to mitigate susceptibility to acute inflammatory lung diseases in individuals with AUD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70088","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T23:59:49Z","timestamp":1748563189000},"page":"1424-1434","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ethanol\u2010induced Nrf2 suppression in the lung is mediated by <scp>AP<\/scp>\u20101\u2010driven expression of mi<scp>R<\/scp>\u2010144"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-5900","authenticated-orcid":false,"given":"Viranuj","family":"Sueblinvong","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine Emory University School of Medicine  Atlanta Georgia 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