{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T14:17:59Z","timestamp":1773497879446,"version":"3.50.1"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:p>Small\u2010for\u2010size syndrome (SFSS) is a common complication following partial liver transplantation and extended hepatectomy. SFSS is characterized by postoperative liver dysfunction caused by insufficient regenerative capacity and portal hyperperfusion and is more frequent in patients with preexisting liver disease. We explored the effect of the Mesenchymal\u2010epithelial transition factor (MET)\u2010agonistic antibody 71D6 on liver regeneration and functional recovery in a mouse model of SFSS. Male C57\/BL6 mice were exposed to repeated carbon tetrachloride injections for 10\u00a0weeks and then randomized into 2 arms receiving 3\u00a0mg\/kg 71D6 or a control immunoglobulin G (IgG). At 2 days after the randomization, the mice were subjected to 70% hepatectomy. Mouse survival was recorded up to 28\u00a0days after hepatectomy. Satellite animals were euthanized at different time points to analyze liver regeneration, fibrosis, and inflammation. Serum 71D6 administration significantly decreased mouse mortality consequent to insufficient regeneration of the cirrhotic liver. Analysis of liver specimens in satellite animals revealed that 71D6 promoted powerful activation of the extracellular signal\u2010regulated kinase pathway and accelerated liver regeneration, characterized by increased liver\u2010to\u2010body weight, augmented mitotic index, and higher serum albumin levels. Moreover, 71D6 accelerated the resolution of hepatic fibrosis as measured by picrosirius red, desmin, and \u03b1\u2013smooth muscle actin staining, and suppressed liver infiltration by macrophages as measured by CD68 and F4\/80 staining. Analysis of gene expression by reverse\u2010transcription polymerase chain reaction confirmed that 71D6 administration suppressed the expression of key profibrotic genes, including platelet\u2010derived growth factor, tissue inhibitor of metalloproteinase 3, and transforming growth factor\u2010\u03b21, and of key proinflammatory genes, including tumor necrosis factor\u2010\u03b1, interleukin\u20101\u03b2, chemokine (C\u2010C motif) ligand 3, and chemokine (C\u2010C motif) ligand 5. These results suggest that activating the MET pathway via an hepatocyte growth factor\u2013mimetic antibody may be beneficial in patients with SFSS and possibly other types of acute and chronic liver disorders.<\/jats:p>","DOI":"10.1002\/lt.26301","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T13:34:20Z","timestamp":1631799260000},"page":"782-793","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["A Mesenchymal\u2010Epithelial Transition Factor\u2010Agonistic Antibody Accelerates Cirrhotic Liver Regeneration and Improves Mouse Survival Following Partial Hepatectomy"],"prefix":"10.1097","volume":"28","author":[{"given":"Kuai","family":"Ma","sequence":"first","affiliation":[{"name":"Division of Transplantation Immunology,National Research Institute for Child Health and Development,Tokyo,Japan"},{"name":"Department of Gastroenterology and Hepatology,Jing\u2019an District Central Hospital,Jing\u2019an Branch of Huashan Hospital,Fudan University,Shanghai,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weitao","family":"Que","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology,National Research Institute for Child Health and Development,Tokyo,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology,National Research Institute for Child Health and Development,Tokyo,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Zhi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Er\u2010li","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Jing\u2019an District Central Hospital,Jing\u2019an Branch of Huashan Hospital,Fudan University,Shanghai,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Huashan Hospital,Fudan University,Shanghai,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Morello","sequence":"additional","affiliation":[{"name":"AgomAb Therapeutics NV,Gent,Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Cazzanti","sequence":"additional","affiliation":[{"name":"AgomAb Therapeutics NV,Gent,Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Michieli","sequence":"additional","affiliation":[{"name":"AgomAb Therapeutics NV,Gent,Belgium"},{"name":"Molecular Biotechnology Center,University of Torino Medical School,Torino,Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terumi","family":"Takahara","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine,University of Toyama,Toyama,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Kang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology,National Research Institute for Child Health and Development,Tokyo,Japan"},{"name":"Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"lt26301-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.hpb.2019.10.2445","article-title":"A systematic review of small for size syndrome after major hepatectomy and liver transplantation","volume":"22","year":"2020","journal-title":"HPB"},{"key":"lt26301-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.hbpd.2020.06.015","article-title":"Small\u2010for\u2010size syndrome in liver transplantation: definition, pathophysiology and management","volume":"19","year":"2020","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"lt26301-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/01.tp.0000228867.98158.d2","article-title":"Liver regeneration is suppressed in small\u2010for\u2010size liver grafts after transplantation: involvement of c\u2010Jun N\u2010terminal kinase, cyclin D1, and defective energy supply","volume":"82","year":"2006","journal-title":"Transplantation"},{"key":"lt26301-bib-0004-20250824","article-title":"Clinical translation of liver regeneration therapies: a conceptual road map","volume":"175","year":"2020","journal-title":"Biochem Pharmacol"},{"key":"lt26301-bib-0005-20250824","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrgastro.2016.97","article-title":"Liver regeneration\u2014mechanisms and models to clinical application","volume":"13","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"lt26301-bib-0006-20250824","doi-asserted-by":"crossref","first-page":"588","DOI":"10.2183\/pjab.86.588","article-title":"The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine","volume":"86","year":"2010","journal-title":"Proc Jpn Acad Ser B Phys Biol Sci"},{"key":"lt26301-bib-0007-20250824","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3390\/biomedicines2040275","article-title":"HGF\u2010Met pathway in regeneration and drug discovery","volume":"2","year":"2014","journal-title":"Biomedicines"},{"issue":"suppl 1","key":"lt26301-bib-0008-20250824","first-page":"188","article-title":"Hepatocyte growth factor twenty years on: much more than a growth factor","volume":"26","year":"2011","journal-title":"J Gastroenterol Hepatol"},{"key":"lt26301-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/protein\/gzw003","article-title":"Combining somatic mutations present in different in vivo affinity\u2010matured antibodies isolated from immunized Lama glama yields ultra\u2010potent antibody therapeutics","volume":"29","year":"2016","journal-title":"Protein Eng Des Sel"},{"key":"lt26301-bib-0011-20250824","doi-asserted-by":"crossref","first-page":"439","DOI":"10.4161\/mabs.1.5.9496","article-title":"Motavizumab","volume":"1","year":"2009","journal-title":"mAbs"},{"key":"lt26301-bib-0012-20250824","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.hepres.2004.09.002","article-title":"Pharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein","volume":"30","year":"2004","journal-title":"Hepatol Res"},{"key":"lt26301-bib-0013-20250824","article-title":"Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh\u2010HGF) in patients with fulminant hepatitis: a phase I\/II clinical trial, following preclinical studies to ensure safety","volume":"9","year":"2011","journal-title":"J Transl Med"},{"key":"lt26301-bib-0014-20250824","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1136\/gut.50.4.558","article-title":"Attenuated acute liver injury in mice by naked hepatocyte growth factor gene transfer into skeletal muscle with electroporation","volume":"50","year":"2002","journal-title":"Gut"},{"key":"lt26301-bib-0015-20250824","article-title":"Liver regeneration: analysis of the main relevant signaling molecules","volume":"2017","year":"2017","journal-title":"Mediators Inflamm"},{"key":"lt26301-bib-0016-20250824","first-page":"109","article-title":"Liver resection in cirrhotic liver: are there any limits?","volume":"82S","year":"2020","journal-title":"Int J Surg"},{"key":"lt26301-bib-0017-20250824","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1096\/fj.02-0494fje","article-title":"Mutation in collagen\u20101 that confers resistance to the action of collagenase results in failure of recovery from CCl4\u2010induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration","volume":"17","year":"2003","journal-title":"FASEB J"},{"key":"lt26301-bib-0018-20250824","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.tox.2008.08.017","article-title":"Hepatic fibrogenesis: from within and outwith","volume":"254","year":"2008","journal-title":"Toxicology"},{"key":"lt26301-bib-0019-20250824","article-title":"Liver regeneration after hepatectomy and partial liver transplantation","volume":"21","year":"2020","journal-title":"Int J Mol Sci"},{"key":"lt26301-bib-0020-20250824","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1136\/gutjnl-2012-302234","article-title":"The central role of the c\u2010Met pathway in rebuilding the liver","volume":"61","year":"2012","journal-title":"Gut"},{"key":"lt26301-bib-0021-20250824","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1097\/01.TP.0000093466.21749.E3","article-title":"Changes in serum levels of hepatocyte growth factor in patients undergoing adult\u2010to\u2010adult living\u2010donor liver transplantation","volume":"76","year":"2003","journal-title":"Transplantation"},{"key":"lt26301-bib-0022-20250824","doi-asserted-by":"crossref","first-page":"665","DOI":"10.4238\/2013.March.11.14","article-title":"Involvement of ERK1\/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats","volume":"12","year":"2013","journal-title":"Genet Mol Res"},{"key":"lt26301-bib-0023-20250824","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1111\/febs.13665","article-title":"TGF\u2010\u03b2 signalling and liver disease","volume":"283","year":"2016","journal-title":"FEBS J"}],"container-title":["Liver Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lt.26301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lt.26301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/lt.26301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T21:05:07Z","timestamp":1756069507000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/lt.26301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1002\/lt.26301","relation":{},"ISSN":["1527-6465","1527-6473"],"issn-type":[{"value":"1527-6465","type":"print"},{"value":"1527-6473","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]},"assertion":[{"value":"2021-04-12","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-10","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}