{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:22:01Z","timestamp":1790785321447,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"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. Physiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cholestasis is a pathological condition involving obstruction of bile secretion and excretion that results in hepatotoxicity, inflammation, fibrosis, cirrhosis, and eventually liver failure. Common bile duct ligation (BDL) model is a well-established murine model to mimic cholestatic liver fibrosis. We previously reported that cytochrome P450 omega-hydroxylase 4a14 (Cyp4a14) plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD)-related fibrosis. The goal of this study was to determine the role of Cyp4a14 in cholestatic-induced liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 mice were subjected to BDL for 14 days, and Cyp4a14 mRNA and protein levels were examined and compared with those of the sham group. Cyp4a14 knockout mice and adeno-associated virus (AAV)-mediated overexpression of Cyp4a14 in C57BL\/6 mice underwent BDL and liver histology, and key fibrosis markers were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both hepatic Cyp4a14 mRNA and protein levels were markedly reduced in BDL liver compared with the time-matched sham group. Cyp4a14 gene-deficient mice aggravates whereas its overexpression alleviates BDL-induced hepatic fibrosis, which were determined by liver function, liver histology, and levels of key fibrotic markers including \u03b1-smooth muscle actin (\u03b1-SMA), transforming growth factor-\u03b21 (TGF-\u03b21), and collagen 1a2 (Col1a2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cyp4a14 exerts a contrasting role in different hepatic fibrosis models. Strategies that enhance Cyp4a14 activity may be potential strategies to cholestatic related liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2021.688259","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T08:12:30Z","timestamp":1622448750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Sha","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5604\/16652681.1226814","article-title":"Management strategies for liver fibrosis.","volume":"16","author":"Altamirano-Barrera","year":"2017","journal-title":"Ann. 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