{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:31:31Z","timestamp":1789241491401,"version":"build-2803163510"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T00:00:00Z","timestamp":1509926400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T00:00:00Z","timestamp":1509926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>\n                    Liver regeneration (LR) happens after various types of injuries. Unlike the well\u2010studied LR caused by partial hepatectomy (PHx), there is accumulating evidence suggesting that LR during other injuries may result from unknown mechanisms. In this study, we found that insulin\u2010like growth factor 2 (IGF\u20102) was drastically induced following the liver injuries caused by tyrosinemia or long\u2010term treatments of CCl\n                    <jats:sub>4<\/jats:sub>\n                    . However, this was not observed during the early phase of acute liver injuries after PHx or single treatment of CCl\n                    <jats:sub>4<\/jats:sub>\n                    . Remarkably, most IGF\u20102\u2010expressing hepatocytes were located at the histological area around the central vein of the liver lobule after the liver injuries caused either in fumarylacetoacetate hydrolase\u2013deficient mice or in CCl\n                    <jats:sub>4<\/jats:sub>\n                    chronically treated mice. Hepatocyte proliferation\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    was significantly promoted by induced IGF\u20102 overexpression, which could be inhibited by adeno\u2010associated virus\u2013delivered IGF\u20102 short hairpin RNAs or linsitinib, an inhibitor of IGF\u20102 signaling. Proliferating hepatocytes\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    responded to IGF\u20102 through both insulin receptor and IGF\u20101 receptor. IGF\u20102 also significantly promoted DNA synthesis of primary hepatocytes\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . More interestingly, the significantly induced IGF\u20102 was also found to colocalize with glutamine synthetase in the region enriched with proliferating hepatocytes for the liver samples from patients with liver fibrosis.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    IGF\u20102 is produced by pericentral hepatocytes to promote hepatocyte proliferation and repair tissue damage in the setting of chronic liver injury, which is distinct from the signaling that occurs post\u2010PHx. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2017;66:2002\u20132015)\n                  <\/jats:p>","DOI":"10.1002\/hep.29340","type":"journal-article","created":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T08:12:47Z","timestamp":1498551167000},"page":"2002-2015","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["Pericentral hepatocytes produce insulin\u2010like growth factor\u20102 to promote liver regeneration during selected injuries in mice"],"prefix":"10.1097","volume":"66","author":[{"given":"Junlai","family":"Liu","sequence":"first","affiliation":[{"name":"School of Life Science and Technology,ShanghaiTech University,Shanghai,China"},{"name":"Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai,China"},{"name":"University of Chinese Academy of 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Sciences,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Nanfang Hospital,Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology,University of Pennsylvania,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanjiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Nanfang Hospital,Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiajun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology,ShanghaiTech 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