{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:39:25Z","timestamp":1791200365148,"version":"4.2.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":942,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Wnt\/\u03b2-catenin signaling plays an important role in hepatic homeostasis, especially in liver development, regeneration, and cancer, and loss of \u03b2-catenin signaling is often associated with increased apoptosis. To elucidate how \u03b2-catenin may be regulating hepatocyte survival, we investigated the susceptibility of \u03b2-catenin conditional knockout (KO) mice and their wild-type (WT) littermates to Fas and tumor necrosis factor-\u03b1 (TNF-\u03b1), two common pathways of hepatocyte apoptosis. While comparable detrimental effects from Fas activation were observed in WT and KO, a paradoxical survival benefit was observed in KO mice challenged with D-galactosamine\/lipopolysaccharide. KO mice showed significantly lower morbidity and liver injury due to early, robust, and protracted activation of NF-\u03baB in the absence of \u03b2-catenin. Enhanced NF-\u03baB activation in KO mice was associated with increased basal inflammation and Toll-like receptor 4 expression and lack of the p65\/\u03b2-catenin complex in hepatocytes. The p65\/\u03b2-catenin complex in WT livers underwent temporal dissociation allowing for NF-\u03baB activation to regulate hepatocyte survival following TNF-\u03b1-induced hepatic injury. Decrease of total \u03b2-catenin protein but not its inactivation induced p65 activity, whereas \u03b2-catenin stabilization either chemically or due to mutations repressed it in hepatomas in a dose-dependent manner, whereas \u03b2-catenin stabilization repressed it either chemically or due to mutations.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      <jats:bold>The p65\/\u03b2-catenin complex in hepatocytes undergoes dynamic changes during TNF-\u03b1\u2013induced hepatic injury and plays a critical role in NF-\u03baB activation and cell survival. Modulation of \u03b2-catenin levels is a unique mode of regulating NF-\u03baB activity and thus may present novel opportunities in devising therapeutics in specific hepatic injuries.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26042","type":"journal-article","created":{"date-parts":[[2012,9,3]],"date-time":"2012-09-03T03:05:53Z","timestamp":1346641553000},"page":"763-774","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":82,"title":["Beta-Catenin\u2013NF-\u03baB Interactions in Murine Hepatocytes: A Complex to Die for"],"prefix":"10.1097","volume":"57","author":[{"given":"Kari","family":"Nejak-Bowen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satdarshan 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