{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:14:28Z","timestamp":1792656868760,"version":"4.5.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":285,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>Liver cancer is the fifth most common cancer. A highly invasive surgical resection of the liver tumor is the main approach used to eliminate the tumor. Mechanisms that terminate liver regeneration when the liver reaches the original size are not known. The aims of this work were to generate an animal model that fails to stop liver regeneration after surgical resections and elucidate mechanisms that are involved in termination of liver regeneration. Because epigenetic control of liver function has been previously implicated in the regulation of liver proliferation, we generated C\/EBP\u03b1\u2010S193A knockin mice, which have alterations in formation of complexes of C\/EBP family proteins with chromatin remodeling proteins. The C\/EBP\u03b1\u2010S193A mice have altered liver morphology and altered liver function leading to changes of glucose metabolism and blood parameters. Examination of the proliferative capacity of C\/EBP\u03b1\u2010S193A livers showed that livers of S193A mice have a higher rate of proliferation after birth, but stop proliferation at the age of 2 months. These animals have increased liver proliferation in response to liver surgery as well as carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010mediated injury. Importantly, livers of C\/EBP\u03b1\u2010S193A mice fail to stop liver regeneration after surgery when livers reach the original, preresection, size. The failure of S193A livers to stop regeneration correlates with the epigenetic repression of key regulators of liver proliferation C\/EBP\u03b1, p53, FXR, SIRT1, PGC1\u03b1, and TERT by C\/EBP\u03b2\u2010HDAC1 complexes. The C\/EBP\u03b2\u2010HDAC1 complexes also repress promoters of enzymes of glucose synthesis PEPCK and G6Pase. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Proper cooperation of C\/EBP and chromatin remodeling proteins is essential for the termination of liver regeneration after surgery and for maintenance of liver functions. (H<jats:sc>epatology<\/jats:sc> 2015;61:315\u2013325)<\/jats:p>","DOI":"10.1002\/hep.27295","type":"journal-article","created":{"date-parts":[[2014,7,9]],"date-time":"2014-07-09T11:58:04Z","timestamp":1404907084000},"page":"315-325","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":61,"title":["Cooperation of C\/EBP family proteins and chromatin remodeling proteins is essential for termination of liver regeneration"],"prefix":"10.1097","volume":"61","author":[{"given":"Jingling","family":"Jin","sequence":"first","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il\u2010Hwa","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology,College of Veterinary Medicine, Gyeongsang National University,South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Lewis","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Iakova","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Breaux","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Jawanmardi","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubov","family":"Timchenko","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai A.","family":"Timchenko","sequence":"additional","affiliation":[{"name":"Huffington Center on Aging and Departments of Pathology and Immunology and Molecular Physiology and Biophysics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2014,11,20]]},"reference":[{"key":"hep27295-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jhep.2012.04.016","article-title":"Liver regeneration","volume":"57","year":"2012","journal-title":"J Hepatol"},{"issue":"Suppl 1","key":"hep27295-bib-0003-20241017","first-page":"203","article-title":"New concepts in liver regeneration","volume":"26","year":"2011","journal-title":"J Gastroenterol Hepatol"},{"key":"hep27295-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.tem.2009.01.005","article-title":"Aging and liver regeneration","volume":"20","year":"2009","journal-title":"Trends Endocrinol Metab"},{"key":"hep27295-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1476-5926-11-3","article-title":"The genetic regulation of the terminating phase of liver regeneration","volume":"11","year":"2012","journal-title":"Comp Hepatol"},{"issue":"Suppl 2","key":"hep27295-bib-0006-20241017","first-page":"S77","article-title":"Transcriptome temporal and functional analysis of liver regeneration termination","volume":"61","year":"2012","journal-title":"Physiol Res"},{"key":"hep27295-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"e20238","DOI":"10.1371\/journal.pone.0020238","article-title":"Mir\u201034a is upregulated during liver regeneration in rats and is associated with the suppression of hepatocyte proliferation","volume":"6","year":"2011","journal-title":"PLoS One"},{"key":"hep27295-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.febslet.2011.02.031","article-title":"Down\u2010regulation of miR\u201023b may contribute to activation of the TGF\u2010beta1\/Smad3 signalling pathway during the termination stage of liver regeneration","volume":"585","year":"2011","journal-title":"FEBS Lett"},{"key":"hep27295-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/hep.23059","article-title":"Enhanced liver regeneration following changes induced by hepatocyte\u2010specific genetic ablation of integrin\u2010linked kinase","volume":"50","year":"2009","journal-title":"Hepatology"},{"key":"hep27295-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1242\/jcs.02459","article-title":"Molecular stop signs: regulation of cell\u2010cycle arrest by C\/EBP transcription factors","volume":"118","year":"2005","journal-title":"J Cell Sci"},{"key":"hep27295-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1111\/j.1474-9726.2010.00617.x","article-title":"Epigenetic changes play critical role in age\u2010associated dysfunctions of the liver","volume":"9","year":"2010","journal-title":"Aging Cell"},{"key":"hep27295-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1172\/JCI41933","article-title":"Elimination of C\/EBPalpha through the ubiquitin\u2010proteasome system promotes the development of liver cancer in mice","volume":"120","year":"2010","journal-title":"J Clin Invest"},{"key":"hep27295-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1074\/jbc.M113.526780","article-title":"Age\u2010associated change of C\/EBP family proteins causes severe liver injury and acceleration of liver proliferation after CCl4 treatments","volume":"289","year":"2014","journal-title":"J Biol Chem"},{"key":"hep27295-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.celrep.2013.02.009","article-title":"Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis","volume":"3","year":"2013","journal-title":"Cell Rep"},{"key":"hep27295-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"14451","DOI":"10.1074\/jbc.M113.460840","article-title":"Transcriptional and translational regulation of C\/EBPbeta\u2010HDAC1 protein complexes controls different levels of p53, SIRT1, and PGC1alpha proteins at the early and late stages of liver cancer","volume":"288","year":"2013","journal-title":"J Biol Chem"},{"key":"hep27295-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1126\/science.7652557","article-title":"Impaired energy homeostasis in C\/EBPalpha knockout mice","volume":"269","year":"1995","journal-title":"Science"},{"key":"hep27295-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"26179","DOI":"10.1074\/jbc.M803545200","article-title":"HDAC1 promotes liver proliferation in young mice via interactions with C\/EBPbeta","volume":"283","year":"2008","journal-title":"J Biol Chem"},{"key":"hep27295-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"26169","DOI":"10.1074\/jbc.M803544200","article-title":"HDAC1 cooperates with C\/EBPalpha in the inhibition of liver proliferation in old mice","volume":"283","year":"2008","journal-title":"J Biol Chem"},{"key":"hep27295-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/hep.26146","article-title":"Farnesoid X receptor inhibits gankyrin in mouse livers and prevents development of liver cancer","volume":"57","year":"2013","journal-title":"Hepatology"},{"key":"hep27295-bib-0020-20241017","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/hep.23794","article-title":"Suppression of liver regeneration and hepatocyte proliferation in glypican 3 hepatocyte\u2010target transgenic mice","volume":"52","year":"2010","journal-title":"Hepatology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.27295","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201501000-00038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:50:52Z","timestamp":1729212652000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201501000-00038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,20]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.27295","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,20]]},"assertion":[{"value":"2014-02-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-30","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}