{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:42:10Z","timestamp":1790674930471,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>\n                    Liver X receptor\u2010alpha (LXR\u03b1) acts as a double\u2010edged sword in different biological situations. Given the elusive role of LXR\u03b1 in hepatocyte viability, this study investigated whether LXR\u03b1 protects hepatocytes from injurious stimuli and the underlying basis. LXR\u03b1 activation prevented hepatocyte apoptosis from CCl\n                    <jats:sub>4<\/jats:sub>\n                    challenges in mice. Consistently, LXR\u03b1 protected hepatocytes specifically from transforming growth factor\u2010beta (TGF\u2010\u03b2), whereas LXR\u03b1 deficiency aggravated TGF\u2010\u03b2\u2010induced hepatocyte injury. In the Gene Expression Omnibus database analysis for LXR\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, TGF\u2010\u03b2 receptors were placed in the core network. Hierarchical clustering and correlation analyses enabled us to find cannabinoid receptor 2 (CB2) as a gene relevant to LXR\u03b1. In human fibrotic liver samples, both LXR\u03b1 and CB2 were lower in patients with septal fibrosis and cirrhosis than those with portal fibrosis. LXR\u03b1 transcriptionally induced CB2; CB2 then defended hepatocytes from TGF\u2010\u03b2. In a macrophage depletion model, JWH133 (a CB2 agonist) treatment prevented toxicant\u2010induced liver injury. MicroRNA 27b (miR\u201027b) was identified as an inhibitor of ubiquitin\u2010specific peptidase 4 (USP4), deubiquitylating TGF\u2010\u03b2 receptor 1 (T\u03b2RI), downstream from CB2. Liver\u2010specific overexpression of LXR\u03b1 protected hepatocytes from injurious stimuli and attenuated hepatic inflammation and fibrosis.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : LXR\u03b1 exerts a cytoprotective effect against TGF\u2010\u03b2 by transcriptionally regulating the CB2 gene in hepatocytes, and CB2 then inhibits USP4\u2010stabilizing T\u03b2RI through miR\u201027b. Our data provide targets for the treatment of acute liver injury.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1415","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T07:39:46Z","timestamp":1564990786000},"page":"1373-1387","source":"Crossref","is-referenced-by-count":22,"title":["Liver X Receptor \u03b1\u2013Induced Cannabinoid Receptor 2 Inhibits Ubiquitin\u2010Specific Peptidase 4 Through miR\u201027b, Protecting Hepatocytes From TGF\u2010\u03b2"],"prefix":"10.1097","volume":"3","author":[{"given":"Hong Min","family":"Wu","sequence":"first","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayoung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja Hyun","family":"Koo","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Sung","family":"Joo","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Geon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences,Seoul National 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