{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T10:01:28Z","timestamp":1769767288541,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Liver fibrosis, a chronic process caused by various pathogenic factors, including drug toxicity, metabolic disorders, and chronic inflammation, is associated with liver-related mortality rates worldwide. It has been established that methotrexate (MTX), a pharmaceutical agent utilised in the treatment of numerous diseases, induces hepatic fibrosis. Currently, there is still a paucity of clinically efficacious antifibrotic drugs for the management of hepatic fibrosis. Thus, the present research sought to evaluate the antifibrotic effects of baricitinib in a rat model of MTX-induced liver fibrosis through the yes-associated protein (YAP) pathway. Materials and Methods: A total of 36 Wistar rats were assigned to three groups (n = 12) randomly: a control group, an MTX-induced liver fibrosis group, and a baricitinib-treated group, which received 20 mg\/kg\/day of baricitinib following fibrosis induction. All treatments were administered for 10 days. Results: Biochemical analyses revealed significant increases in plasma alanine aminotransferase (ALT), cytokeratin-18 (CK-18), and malondialdehyde (MDA) levels, as well as liver transforming growth factor-beta (TGF-\u03b2), YAP1, and MDA levels, in the MTX-induced fibrosis group in comparison to the control group (p &lt; 0.05). Notably, baricitinib addition significantly reduced these biomarkers (p &lt; 0.05). A histopathological evaluation further confirmed a marked reduction in fibrosis, hepatic necrosis, and cellular infiltration in the baricitinib-treated group relative to the MTX-induced fibrosis group. Conclusions: Accordingly, our findings suggest that baricitinib mitigates MTX-induced liver fibrosis, potentially through its anti-inflammatory and antifibrotic effects mediated by the suppression of the YAP signalling pathway. These results highlight that baricitinib could be a potential treatment option for patients with liver fibrosis.<\/jats:p>","DOI":"10.3390\/medicina61050857","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:38:06Z","timestamp":1746531486000},"page":"857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Baricitinib Mitigates Methotrexate-Induced Liver Fibrosis Model via YAP Pathway"],"prefix":"10.3390","volume":"61","author":[{"given":"Mehmet","family":"Ulusan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur 15030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-444X","authenticated-orcid":false,"given":"Mumin Alper","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Izmir Katip Celebi University, Izmir 35620, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-9382","authenticated-orcid":false,"given":"Ozkan","family":"Simsek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur 15030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zafer","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Veterinary Medicine, Tekirdag Namik Kemal University, Tekirdag 59010, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertug Bekir","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery, Health Science Institute, Erciyes University, Kayseri 38280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gultekin","family":"Atalan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Veterinary Medicine, Erciyes University, Kayseri 38280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oytun","family":"Erbas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, BAMER, Biruni University, Istanbul 34015, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.jhep.2020.11.045","article-title":"Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease","volume":"74","author":"Robert","year":"2021","journal-title":"J. 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