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MicroRNA (miR)-1946a is predicted to bind to the TGF\u03b21 3\u2032 untranslated region (UTR), thereby inhibiting its transcription. We hypothesize that alcohol suppresses miR-1946a and induces TGF\u03b21. Primary murine lung fibroblasts (PLFs) were cultured\u2009\u00b1\u2009alcohol, miR-1946a mimic or inhibitor, and TGF\u03b21 signaling inhibitors. miR-1946a was analyzed after alcohol treatment in vitro and in vivo. TGF\u03b21 expression and TGF\u03b21 3\u2032UTR-luciferase activity was quantified. We showed that alcohol suppressed miR-1946a in the alcohol-fed mouse lungs and PLFs. MiR-1946a inhibitor increased TGF\u03b21 expression in the fibroblast. MiR-1946a mimic treatment suppressed TGF\u03b21 gene expression and TGF\u03b21 3\u2032UTR activity. Overexpression of miR1946a inhibited alcohol-induced TGF\u03b21 gene and protein expression as well as alcohol-induced TGF\u03b21 and \u03b1-smooth muscle actin (SMA) protein expression in PLFs. In conclusion, miR-1946a modulates TGF\u03b21 expression through direct interaction with TGF\u03b21 3\u2032UTR. These findings identify a novel mechanism by which alcohol induces TGF\u03b21 in the lung.<\/jats:p>","DOI":"10.1038\/s41598-020-76148-5","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T11:03:19Z","timestamp":1604574199000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Alcohol induces TGF\u03b21 via downregulation of miR-1946a in murine lung fibroblast"],"prefix":"10.1038","volume":"10","author":[{"given":"Xian","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen T.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mevelyn J.","family":"Kaalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-5900","authenticated-orcid":false,"given":"Viranuj","family":"Sueblinvong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"76148_CR1","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1586\/ers.10.62","volume":"4","author":"A Gardner","year":"2010","unstructured":"Gardner, A., Borthwick, L. 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