{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:16:42Z","timestamp":1789906602692,"version":"4.0.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"tdm","delay-in-days":0,"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":[[2020,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>STAT3, a member of the signal transducer and activator of transcription (STAT) family, is strongly associated with liver injury, inflammation, regeneration, and hepatocellular carcinoma development. However, the signals that regulate STAT3 activity are not completely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Here we characterize CREB\/ATF bZIP transcription factor CREBZF as a critical regulator of STAT3 in the hepatocyte to repress liver regeneration. We show that CREBZF deficiency stimulates the expression of the cyclin gene family and enhances liver regeneration after partial hepatectomy. Flow cytometry analysis reveals that CREBZF regulates cell cycle progression during liver regeneration in a hepatocyte\u2010autonomous manner. Similar results were observed in another model of liver regeneration induced by intraperitoneal injection of carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      ). Mechanistically, CREBZF potently associates with the linker domain of STAT3 and represses its dimerization and transcriptional activity\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Importantly, hepatectomy\u2010induced hyperactivation of cyclin D1 and liver regeneration in CREBZF liver\u2010specific knockout mice was reversed by selective STAT3 inhibitor cucurbitacin I. In contrast, adeno\u2010associated virus\u2013mediated overexpression of CREBZF in the liver inhibits the expression of the cyclin gene family and attenuates liver regeneration in CCl\n                      <jats:sub>4<\/jats:sub>\n                      \u2010treated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results characterize CREBZF as a coregulator of STAT3 to inhibit regenerative capacity, which may represent an essential cellular signal to maintain liver mass homeostasis. Therapeutic approaches to inhibit CREBZF may benefit the compromised liver during liver transplantation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.30919","type":"journal-article","created":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T05:34:07Z","timestamp":1567143247000},"page":"1421-1436","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":52,"title":["CREBZF as a Key Regulator of STAT3 Pathway in the Control of Liver Regeneration in Mice"],"prefix":"10.1097","volume":"71","author":[{"given":"Zhimin","family":"Hu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamei","family":"Han","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Xinhua Hospital, Shanghai Jiaotong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengguang","family":"Ma","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoyuan","family":"Cui","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshuai","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Xue","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences, Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyun","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,Zhongshan Hospital, Fudan University,Shanghai,China"},{"name":"Fudan Institute for Metabolic Diseases,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifu","family":"Wu","sequence":"additional","affiliation":[{"name":"Metabolic and Bariatric Surgery of Department of General Surgery,Zhongshan Hospital, Fudan University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,Zhongshan Hospital, Fudan University,Shanghai,China"},{"name":"Fudan Institute for Metabolic Diseases,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. Eugene","family":"Chin","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences,Soochow University Medical College,Suzhou,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Key Laboratory of Immune Microenvironment and Disease, School of Basic Medical Sciences,Tianjin Medical University,Tianjin,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxian","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2605-5697","authenticated-orcid":false,"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology,the First Affiliated Hospital, Institute for Liver 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