{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:51:16Z","timestamp":1772992276204,"version":"3.50.1"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T00:00:00Z","timestamp":1415318400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0112384","type":"journal-article","created":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T18:59:56Z","timestamp":1415386796000},"page":"e112384","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":51,"title":["Mutant MMP-9 and HGF Gene Transfer Enhance Resolution of CCl4-Induced Liver Fibrosis in Rats: Role of ASH1 and EZH2 Methyltransferases Repression"],"prefix":"10.1371","volume":"9","author":[{"given":"Hussein","family":"Atta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"El-Rehany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olfat","family":"Hammam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hend","family":"Abdel-Ghany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Ramzy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Roderfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Roeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman","family":"Al-Hendy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salama Abdel","family":"Raheim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatem","family":"Allam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba","family":"Marey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,11,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1002\/hep.25915","article-title":"New therapeutic paradigm for patients with cirrhosis","volume":"56","author":"EA Tsochatzis","year":"2012","journal-title":"Hepatology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3748\/wjg.v12.i4.509","article-title":"Molecular therapy for hepatic injury and fibrosis: where are we?","volume":"12","author":"CC Prosser","year":"2006","journal-title":"World J Gastroenterol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/hep.510240129","article-title":"Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis","volume":"24","author":"JP Iredale","year":"1996","journal-title":"Hepatology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1177\/1756283X11413002","article-title":"Current status of novel antifibrotic therapies in patients with chronic liver disease","volume":"4","author":"M Cohen-Naftaly","year":"2011","journal-title":"Therap Adv Gastroenterol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1172\/JCI1018","article-title":"Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors","volume":"102","author":"JP Iredale","year":"1998","journal-title":"J Clin Invest"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1096\/fj.05-4828com","article-title":"Inhibition of hepatic fibrogenesis by matrix metalloproteinase-9 mutants in mice","volume":"20","author":"M Roderfeld","year":"2006","journal-title":"FASEB J"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"11069","DOI":"10.1074\/jbc.M111490200","article-title":"Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis","volume":"277","author":"FR Murphy","year":"2002","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1053\/jhep.2002.35625","article-title":"Tissue inhibitor of metalloproteinases-1 attenuates spontaneous liver fibrosis resolution in the transgenic mouse","volume":"36","author":"H Yoshiji","year":"2002","journal-title":"Hepatology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1749-6632.1994.tb24722.x","article-title":"Regulation of matrix metalloproteinase activity","volume":"732","author":"G Murphy","year":"1994","journal-title":"Ann N Y Acad Sci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"14967","DOI":"10.1016\/S0021-9258(17)36561-4","article-title":"Analysis of the role of the COOH-terminal domain in the activation, proteolytic activity, and tissue inhibitor of metalloproteinase interactions of gelatinase B","volume":"269","author":"JP O'Connell","year":"1994","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1096\/fj.99-0947fje","article-title":"An MMP-9 mutant without gelatinolytic activity as a novel TIMP-1-antagonist","volume":"14","author":"E Roeb","year":"2000","journal-title":"FASEB J"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(95)90279-1","article-title":"Hepatocyte growth factor: a multifunctional cytokine","volume":"345","author":"P Boros","year":"1995","journal-title":"Lancet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1111\/j.1478-3231.2009.02056.x","article-title":"Low-dose simultaneous delivery of adenovirus encoding hepatocyte growth factor and vascular endothelial growth factor in dogs enhances liver proliferation without systemic growth factor elevation","volume":"29","author":"HM Atta","year":"2009","journal-title":"Liver Int"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/0270-9139(93)90237-H","article-title":"Stimulation of liver growth by exogenous human hepatocyte growth factor in normal and partially hepatectomized rats","volume":"18","author":"K Fujiwara","year":"1993","journal-title":"Hepatology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/hep.510260111","article-title":"Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis\/cirrhosis","volume":"26","author":"Y Matsuda","year":"1997","journal-title":"Hepatology"},{"key":"ref16","first-page":"1641","article-title":"Simultaneous transfer of vascular endothelial growth factor and hepatocyte growth factor genes effectively promotes liver regeneration after hepatectomy in cirrhotic rats","volume":"51","author":"H Oe","year":"2004","journal-title":"Hepatogastroenterology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/hep.510240328","article-title":"Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats","volume":"24","author":"H Yasuda","year":"1996","journal-title":"Hepatology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.surg.2006.10.006","article-title":"Adenoviral vector expressing hepatocyte growth factor promotes liver regeneration by preoperative injection: the advantages of performing selective injection to the remnant lobe","volume":"141","author":"M Ueno","year":"2007","journal-title":"Surgery"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/hep.1840160520","article-title":"Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo","volume":"16","author":"Y Ishiki","year":"1992","journal-title":"Hepatology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1006\/jsre.1998.5472","article-title":"Hepatocyte growth factor prevents lipopolysaccharide-induced hepatic sinusoidal endothelial cell injury and intrasinusoidal fibrin deposition in rats","volume":"80","author":"S Seto","year":"1998","journal-title":"J Surg Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/BF03401777","article-title":"Intravenous injection of an adenovirus encoding hepatocyte growth factor results in liver growth and has a protective effect against apoptosis","volume":"6","author":"D Phaneuf","year":"2000","journal-title":"Mol Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.surg.2008.04.011","article-title":"Hepatocyte growth factor improves survival after partial hepatectomy in cirrhotic rats suppressing apoptosis of hepatocytes","volume":"144","author":"M Nishino","year":"2008","journal-title":"Surgery"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1006\/bbrc.2000.3793","article-title":"Adenovirus-mediated hepatocyte growth factor gene transfer prevents lethal liver failure in rats","volume":"278","author":"T Nomi","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/5593","article-title":"Hepatocyte growth factor gene therapy of liver cirrhosis in rats","volume":"5","author":"T Ueki","year":"1999","journal-title":"Nat Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1111\/j.1523-1755.2000.00375.x","article-title":"Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways","volume":"58","author":"Y Liu","year":"2000","journal-title":"Kidney Int"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1128\/MCB.00993-07","article-title":"Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes","volume":"27","author":"GD Gregory","year":"2007","journal-title":"Mol Cell Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature01080","article-title":"Active genes are tri-methylated at K4 of histone H3","volume":"419","author":"H Santos-Rosa","year":"2002","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/hep.25754","article-title":"Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation","volume":"56","author":"MJ Perugorria","year":"2012","journal-title":"Hepatology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.gde.2004.02.001","article-title":"The functions of E(Z)\/EZH2-mediated methylation of lysine 27 in histone H3","volume":"14","author":"R Cao","year":"2004","journal-title":"Curr Opin Genet Dev"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e74870","DOI":"10.1371\/journal.pone.0074870","article-title":"Effects of EZH2 polymorphisms on susceptibility to and pathological development of hepatocellular carcinoma","volume":"8","author":"YL Yu","year":"2013","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"G881","DOI":"10.1152\/ajpgi.00289.2013","article-title":"Evidence for and against epithelial-to-mesenchymal transition in the liver","volume":"305","author":"G Xie","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1053\/j.gastro.2009.10.002","article-title":"MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis","volume":"138","author":"J Mann","year":"2010","journal-title":"Gastroenterology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jhep.2013.05.039","article-title":"Epigenetic modifications as new targets for liver disease therapies","volume":"59","author":"M Zeybel","year":"2013","journal-title":"J Hepatol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1067\/mob.2000.104837","article-title":"Ovarian cancer gene therapy: repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model","volume":"182","author":"A Al-Hendy","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1172\/JCI30542","article-title":"Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ","volume":"117","author":"JP Iredale","year":"2007","journal-title":"J Clin Invest"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1002\/hep.23123","article-title":"Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies","volume":"50","author":"Y Popov","year":"2009","journal-title":"Hepatology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.surg.2005.10.003","article-title":"Combination gene therapy of HGF and truncated type II TGF-beta receptor for rat liver cirrhosis after partial hepatectomy","volume":"139","author":"S Ozawa","year":"2006","journal-title":"Surgery"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0076-6879(83)91014-5","article-title":"Determination of total protein","volume":"91","author":"GL Peterson","year":"1983","journal-title":"Methods Enzymol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1097\/00000478-199512000-00007","article-title":"Chronic hepatitis. An update on terminology and reporting","volume":"19","author":"KP Batts","year":"1995","journal-title":"Am J Surg Pathol"},{"key":"ref40","first-page":"560345","article-title":"Establishment of a standardized liver fibrosis model with different pathological stages in rats","volume":"2012","author":"L Li","year":"2012","journal-title":"Gastroenterol Res Pract"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/hep.1840210328","article-title":"Increased expression of matrix metalloproteinase-II in experimental liver fibrosis in rats","volume":"21","author":"T Takahara","year":"1995","journal-title":"Hepatology"},{"key":"ref42","first-page":"1114","article-title":"Expression of matrix metalloproteinases in spontaneous regression of liver fibrosis","volume":"48","author":"HS Lee","year":"2001","journal-title":"Hepatogastroenterology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e53392","DOI":"10.1371\/journal.pone.0053392","article-title":"Truncated active human matrix metalloproteinase-8 delivered by a chimeric adenovirus-hepatitis B virus vector ameliorates rat liver cirrhosis","volume":"8","author":"J Liu","year":"2013","journal-title":"PLoS One"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3748\/wjg.v9.i2.316","article-title":"Inhibition on the production of collagen type I, III of activated hepatic stellate cells by antisense TIMP-1 recombinant plasmid","volume":"9","author":"WB Liu","year":"2003","journal-title":"World J Gastroenterol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1002\/hep.20425","article-title":"Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats","volume":"40","author":"CJ Parsons","year":"2004","journal-title":"Hepatology"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1053\/j.gastro.2008.01.014","article-title":"Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7","volume":"134","author":"Y Inagaki","year":"2008","journal-title":"Gastroenterology"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S0002-9440(10)62323-1","article-title":"Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis","volume":"166","author":"WH Kim","year":"2005","journal-title":"Am J Pathol"},{"key":"ref48","first-page":"857","article-title":"Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats","volume":"17","author":"H Inoue","year":"2006","journal-title":"Int J Mol Med"},{"key":"ref49","first-page":"60","article-title":"Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: its specific receptor c-met does","volume":"24","author":"A D'Errico","year":"1996","journal-title":"Hepatology"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1006\/excr.1998.4107","article-title":"Constitutive expression of HGF modulates renal epithelial cell phenotype and induces c-met and fibronectin expression","volume":"242","author":"Y Liu","year":"1998","journal-title":"Exp Cell Res"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/S0002-9440(10)62514-X","article-title":"Hepatocyte growth factor\/scatter factor released during peritonitis is active on mesothelial cells","volume":"159","author":"T Rampino","year":"2001","journal-title":"Am J Pathol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"C554","DOI":"10.1152\/ajpcell.1995.269.3.C554","article-title":"Relationships between mesangial cell proliferation and types I and IV collagen mRNA levels in vitro","volume":"269","author":"CJ He","year":"1995","journal-title":"Am J Physiol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1091\/mbc.3.10.1057","article-title":"The extracellular regulation of growth factor action","volume":"3","author":"R Flaumenhaft","year":"1992","journal-title":"Mol Biol Cell"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/08977190902834077","article-title":"The antifibrogenic effect of hepatocyte growth factor (HGF) on renal tubular (HK-2) cells is dependent on cell growth","volume":"27","author":"C Esposito","year":"2009","journal-title":"Growth Factors"},{"key":"ref55","first-page":"503","article-title":"Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats","volume":"17","author":"K Kusumoto","year":"2006","journal-title":"Int J Mol Med"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1440-1681.2011.05483.x","article-title":"Recombinant human HGF, but not rat HGF, elicits glomerular injury and albuminuria in normal rats via an immune complex-dependent mechanism","volume":"38","author":"S Mizuno","year":"2011","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1073\/pnas.87.8.3200","article-title":"Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues","volume":"87","author":"K Tashiro","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biochi.2006.07.009","article-title":"The control of histone lysine methylation in epigenetic regulation","volume":"89","author":"P Volkel","year":"2007","journal-title":"Biochimie"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"11392","DOI":"10.1074\/jbc.M310284200","article-title":"Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells","volume":"279","author":"S Hazra","year":"2004","journal-title":"J Biol Chem"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1002\/hep.24792","article-title":"Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator-activated receptor gamma in hepatic stellate cells for their antifibrotic effect","volume":"55","author":"MD Yang","year":"2012","journal-title":"Hepatology"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0112384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T16:02:59Z","timestamp":1747152179000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0112384"}},"subtitle":[],"editor":[{"given":"Matias A.","family":"Avila","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,11,7]]},"references-count":60,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0112384","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,7]]}}}