{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:47:13Z","timestamp":1790282833693,"version":"4.1.0"},"reference-count":33,"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":396,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030-142884"],"award-info":[{"award-number":["310030-142884"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"ETH Zurich","doi-asserted-by":"crossref","award":["0-23123-08"],"award-info":[{"award-number":["0-23123-08"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The nuclear factor erythroid-derived 2, like 2 (Nrf2) transcription factor is a key regulator of the antioxidant defense system, and pharmacological activation of Nrf2 is a promising strategy for prevention of toxin-induced liver damage. However, the consequences of Nrf2 activation on liver regeneration (LR) have not been determined. To address this question, we generated mice expressing a constitutively active Nrf2 (caNrf2) mutant in hepatocytes. Expression of the transgene did not affect liver homeostasis. Surprisingly, however, there was no beneficial effect of Nrf2 activation on CCl\n                      <jats:sub>4<\/jats:sub>\n                      -induced liver injury and fibrosis. Most important, LR after partial hepatectomy was impaired in caNrf2-transgenic mice as a result of delayed hepatocyte proliferation and enhanced apoptosis of these cells after liver injury. Mechanistically, this involved up-regulation of the cyclin-dependent kinase inhibitor p15 and the proapoptotic protein Bcl2l11 (Bim). Using chromatin immunoprecipitation, we show that the\n                      <jats:italic toggle=\"yes\">p15<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Bcl2l11<\/jats:italic>\n                      genes are direct targets of Nrf2, which are activated under hyperproliferative conditions in the liver.\n                      <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                      : Activated Nrf2 delays proliferation and induces apoptosis of hepatocytes in the regenerating liver. These negative effects of Nrf2 activation on LR should be considered when Nrf2-activating compounds are used for prevention of liver damage. (Hepatology 2014;60:670\u2013678)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26964","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T02:36:39Z","timestamp":1386297399000},"page":"670-678","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":75,"title":["Activated Nrf2 impairs liver regeneration in mice by activation of genes involved in cell-cycle control and apoptosis"],"prefix":"10.1097","volume":"60","author":[{"given":"Ulrike 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