{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:38:28Z","timestamp":1782394708128,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Cyclooxygenase\u20102 (COX\u20102) is involved in different liver diseases, but little is known about the significance of COX\u20102 in cholestatic injury. This study was designed to elucidate the role of COX\u20102 expression in hepatocytes during the pathogenesis of obstructive cholestasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used genetically modified mice constitutively expressing human COX\u20102 in hepatocytes. Transgenic mice (<jats:italic>hCOX\u20102\u2010Tg<\/jats:italic>) and their wild\u2010type (<jats:italic>Wt<\/jats:italic>) littermates were either subjected to a mid\u2010abdominal laparotomy or common bile duct ligation (BDL) for 2 or 5\u2009days. Then, we explored the mechanisms underlying the role of COX\u20102 and its derived prostaglandins in liver function, and the synthesis and excretion of bile acids (BA) in response to cholestatic liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After BDL, <jats:italic>hCOX\u20102\u2010Tg<\/jats:italic> mice showed lower grades of hepatic necrosis and inflammation than <jats:italic>Wt<\/jats:italic> mice, in part by a reduced hepatic neutrophil recruitment associated with lower mRNA levels of pro\u2010inflammatory cytokines. Furthermore, <jats:italic>hCOX\u20102\u2010Tg<\/jats:italic> mice displayed a differential metabolic pattern of BA synthesis that led to an improved clearance after BDL\u2010induced accumulation. In addition, an enhanced response to the BDL\u2010induced oxidative stress and hepatic apoptosis was observed. In\u00a0vitro experiments using hepatic cells that stably express hCOX\u20102 confirmed the cytoprotective role of prostaglandin E<jats:sub>2<\/jats:sub> against BA toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, our data indicate that constitutive expression of COX\u20102 in hepatocytes ameliorates cholestatic liver injury in mice by reducing inflammation and cell damage and by modulating BA metabolism, pointing to a role for COX\u20102 as a defensive response against cholestasis\u2010derived BA accumulation and injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16004","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T09:00:18Z","timestamp":1717750818000},"page":"2409-2423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Beneficial effects of hepatic cyclooxygenase\u20102 expression against cholestatic injury after common bile duct ligation in mice"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-4045","authenticated-orcid":false,"given":"Roc\u00edo","family":"Brea","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols\u2010Morreale (IIBM), CSIC\u2010UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-4886","authenticated-orcid":false,"given":"Natalia","family":"Casanova","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols\u2010Morreale (IIBM), CSIC\u2010UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-2111","authenticated-orcid":false,"given":"Carlota","family":"Alvarez\u2010Lucena","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols\u2010Morreale (IIBM), CSIC\u2010UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8146-6165","authenticated-orcid":false,"given":"Marina","family":"Fuertes\u2010Agudo","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Valencia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3074-9197","authenticated-orcid":false,"given":"Mar\u00eda","family":"Luque\u2010Tevar","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Valencia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-3861","authenticated-orcid":false,"given":"Carme","family":"Cucarella","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Valencia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-5828","authenticated-orcid":false,"given":"Mar\u00eda C.","family":"Capitani","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental (IFISE\u2010CONICET)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-2330","authenticated-orcid":false,"given":"Mar\u00eda V.","family":"Marinochi","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental (IFISE\u2010CONICET)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2024-7046","authenticated-orcid":false,"given":"Mat\u00edas E.","family":"Fusini","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Histolog\u00eda y Embriolog\u00eda Humana\u2010Fac. 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