{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T02:03:04Z","timestamp":1774922584695,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Life, Health &amp; Environmental Sciences, University of L\u2019Aquila","award":["FFO MeSVA 2023\u2014PSD2303"],"award-info":[{"award-number":["FFO MeSVA 2023\u2014PSD2303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-\u03b21 (TGF-\u03b21). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, \u03b1-SMA, pSmad2\/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-\u03b21 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-\u03b21-induced EMT process on Caco-2 IEC by increasing occludin and decreasing \u03b1-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.<\/jats:p>","DOI":"10.3390\/ijms25168862","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T10:28:41Z","timestamp":1723631321000},"page":"8862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models"],"prefix":"10.3390","volume":"25","author":[{"given":"Serena","family":"Artone","sequence":"first","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"},{"name":"PhD School in Medicine and Public Health, Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7862-3323","authenticated-orcid":false,"given":"Alessia","family":"Ciafarone","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"},{"name":"PhD School in Health & Environmental Sciences, Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Rosaria","family":"Augello","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0551-5076","authenticated-orcid":false,"given":"Francesca","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-5445","authenticated-orcid":false,"given":"Maria Grazia","family":"Cifone","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-2691","authenticated-orcid":false,"given":"Paola","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Cinque","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6341-5711","authenticated-orcid":false,"given":"Giovanni","family":"Latella","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"},{"name":"Unit of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health & Environmental Sciences, University of L\u2019Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, Coppito, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41575-021-00543-0","article-title":"Revisiting fibrosis in inflammatory bowel disease: The gut thickens","volume":"19","author":"Ungaro","year":"2022","journal-title":"Nat. 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