{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:36:55Z","timestamp":1790980615748,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","gastrojournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Gastroenterology"],"published-print":{"date-parts":[[2009,10]]},"DOI":"10.1053\/j.gastro.2009.06.051","type":"journal-article","created":{"date-parts":[[2009,7,4]],"date-time":"2009-07-04T04:12:50Z","timestamp":1246680770000},"page":"1478-1488.e8","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":233,"title":["Hedgehog-Mediated Epithelial-to-Mesenchymal Transition and Fibrogenic Repair in Nonalcoholic Fatty Liver Disease"],"prefix":"10.1053","volume":"137","author":[{"given":"Wing\u2013Kin","family":"Syn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngmi","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Omenetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Abdelmalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Guy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal P.","family":"Witek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin M.","family":"Fearing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago A.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Teaberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve S.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Conde\u2013Vancells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze F.","family":"Karaca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Mae","family":"Diehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1053\/j.gastro.2009.06.051_bib1","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1002\/hep.20214","article-title":"Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells","volume":"39","author":"Fausto","year":"2004","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib2","first-page":"259","article-title":"Ductular reaction and its diagnostic significance","volume":"15","author":"Roskams","year":"1998","journal-title":"Semin Diagn Pathol"},{"key":"10.1053\/j.gastro.2009.06.051_bib3","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1053\/j.gastro.2007.05.012","article-title":"Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction","volume":"133","author":"Richardson","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2009.06.051_bib4","first-page":"3331","article-title":"Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans","volume":"118","author":"Omenetti","year":"2008","journal-title":"J Clin Invest"},{"key":"10.1053\/j.gastro.2009.06.051_bib5","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1053\/gast.2002.33573","article-title":"Nonalcoholic fatty liver disease","volume":"122","author":"Clark","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2009.06.051_bib6","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0016-5085(03)00907-7","article-title":"Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis","volume":"125","author":"Feldstein","year":"2003","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2009.06.051_bib7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/hep.21223","article-title":"In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease","volume":"44","author":"Wieckowska","year":"2006","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib8","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/labinvest.3700689","article-title":"Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice","volume":"87","author":"Fleig","year":"2007","journal-title":"Lab Invest"},{"key":"10.1053\/j.gastro.2009.06.051_bib9","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1073733","article-title":"Medulloblastoma growth inhibition by hedgehog pathway blockade","volume":"297","author":"Berman","year":"2002","journal-title":"Science"},{"key":"10.1053\/j.gastro.2009.06.051_bib10","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/toxsci\/kfn076","article-title":"Dose- and route-dependent teratogenicity, toxicity and pharmacokinetic profiles of the hedgehog signaling antagonist cyclopamine in the mouse","volume":"104","author":"Lipinski","year":"2008","journal-title":"Toxicol Sci"},{"key":"10.1053\/j.gastro.2009.06.051_bib11","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am J Gastroenterol"},{"key":"10.1053\/j.gastro.2009.06.051_bib12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/labinvest.3700537","article-title":"Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation","volume":"87","author":"Omenetti","year":"2007","journal-title":"Lab Invest"},{"key":"10.1053\/j.gastro.2009.06.051_bib13","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/hep.21660","article-title":"Bile ductules and stromal cells express hedgehog ligands and\/or hedgehog target genes in primary biliary cirrhosis","volume":"45","author":"Jung","year":"2007","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jhep.2007.07.032","article-title":"Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells","volume":"48","author":"Yang","year":"2008","journal-title":"J Hepatol"},{"key":"10.1053\/j.gastro.2009.06.051_bib15","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/s11626-998-0106-x","article-title":"Primary culture of cholangiocytes from normal mouse liver","volume":"34","author":"Yahagi","year":"1998","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"10.1053\/j.gastro.2009.06.051_bib16","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1053\/j.gastro.2005.01.055","article-title":"Inducible nitric oxide synthase up-regulates Notch-1 in mouse cholangiocytes: implications for carcinogenesis","volume":"128","author":"Ishimura","year":"2005","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2009.06.051_bib17","doi-asserted-by":"crossref","first-page":"G859","DOI":"10.1152\/ajpgi.00456.2005","article-title":"Hedgehog signaling maintains resident hepatic progenitors throughout life","volume":"290","author":"Sicklick","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1053\/j.gastro.2009.06.051_bib18","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1101\/gad.1025302","article-title":"Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened","volume":"16","author":"Chen","year":"2002","journal-title":"Genes Dev"},{"key":"10.1053\/j.gastro.2009.06.051_bib19","first-page":"303","article-title":"Development and characterization of polarized primary cultures of rat intrahepatic bile duct epithelial cells","volume":"74","author":"Vroman","year":"1996","journal-title":"Lab Invest"},{"key":"10.1053\/j.gastro.2009.06.051_bib20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J Clin Invest"},{"key":"10.1053\/j.gastro.2009.06.051_bib21","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/nm888","article-title":"BMP-7 counteracts TGF-\u03b21-induced epithelial-to-mesenchymal transition and reverses chronic renal injury","volume":"9","author":"Zeisberg","year":"2003","journal-title":"Nat Med"},{"key":"10.1053\/j.gastro.2009.06.051_bib22","doi-asserted-by":"crossref","first-page":"8094","DOI":"10.1074\/jbc.M413102200","article-title":"Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney","volume":"280","author":"Zeisberg","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1053\/j.gastro.2009.06.051_bib23","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1128\/MCB.24.10.4241-4254.2004","article-title":"xId2 and Id3 define the potency of cell proliferation and differentiation responses to transforming growth factor beta and bone morphogenetic protein","volume":"24","author":"Kowanetz","year":"2003","journal-title":"Mol Cell Biol"},{"key":"10.1053\/j.gastro.2009.06.051_bib24","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/S0016-5085(96)70028-8","article-title":"Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation","volume":"111","author":"Weltman","year":"1996","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2009.06.051_bib25","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0002-9440(10)63489-X","article-title":"Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease","volume":"163","author":"Roskams","year":"2003","journal-title":"Am J Pathol"},{"key":"10.1053\/j.gastro.2009.06.051_bib26","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1053\/jhep.2001.26751","article-title":"A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver","volume":"34","author":"Akhurst","year":"2001","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib27","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/hep.20082","article-title":"Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease","volume":"39","author":"Yang","year":"2004","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib28","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1093\/carcin\/15.12.2747","article-title":"Differentiation of oval cells into duct-like cells in preneoplastic liver of rats placed on a choline-deficient diet supplemented with ethionine","volume":"15","author":"Tee","year":"1994","journal-title":"Carcinogenesis"},{"key":"10.1053\/j.gastro.2009.06.051_bib29","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1038\/labinvest.3700349","article-title":"Role for hedgehog signaling in hepatic stellate cell activation and viability","volume":"85","author":"Sicklick","year":"2005","journal-title":"Lab Invest"},{"key":"10.1053\/j.gastro.2009.06.051_bib30","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s004180050109","article-title":"The oval-shaped cell as a candidate for a liver stem cell in embryonic, neonatal and precancerous liver: identification based on morphology and immunohistochemical staining for albumin and pyruvate kinase isoenzyme expression","volume":"107","author":"Tian","year":"1997","journal-title":"Hisochem Cell Biol"},{"key":"10.1053\/j.gastro.2009.06.051_bib31","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.ceb.2003.10.006","article-title":"Epithelial-mesenchymal transitions in development and pathologies","volume":"15","author":"Thiery","year":"2003","journal-title":"Curr Opin Cell Biol"},{"key":"10.1053\/j.gastro.2009.06.051_bib32","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000147748","article-title":"An overview of epithelio-mesenchymal transformation","volume":"154","author":"Hay","year":"1995","journal-title":"Acta Anat (Basel)"},{"key":"10.1053\/j.gastro.2009.06.051_bib33","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1093\/carcin\/bgm281","article-title":"Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-\u03b2-mediated activation of the ALK5-Smad 3 pathway","volume":"29","author":"Yoo","year":"2008","journal-title":"Carcinogenesis"},{"key":"10.1053\/j.gastro.2009.06.051_bib34","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1083\/jcb.130.2.393","article-title":"Identification and characterization of a fibroblast marker: FSP1","volume":"130","author":"Strutz","year":"1995","journal-title":"J Cell Biol"},{"key":"10.1053\/j.gastro.2009.06.051_bib35","first-page":"F563","article-title":"Early role of Fsp1 in epithelial-mesenchymal transformation","volume":"273","author":"Okada","year":"1997","journal-title":"Am J Physiol"},{"key":"10.1053\/j.gastro.2009.06.051_bib36","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1136\/gut.2006.092460","article-title":"Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats","volume":"56","author":"Kinoshita","year":"2007","journal-title":"Gut"},{"key":"10.1053\/j.gastro.2009.06.051_bib37","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jhep.2004.09.012","article-title":"The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies","volume":"42","author":"Adams","year":"2005","journal-title":"J Hepatol"},{"key":"10.1053\/j.gastro.2009.06.051_bib38","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1002\/jcb.21509","article-title":"Cancer metastasis facilitated by developmental pathways: sonic hedgehog, Notch, and bone morphogenic proteins","volume":"102","author":"Bailey","year":"2007","journal-title":"J Cell Biochem"},{"key":"10.1053\/j.gastro.2009.06.051_bib39","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/hep.22397","article-title":"Murine cirrhosis induces hepatocyte epithelial mesenchymal transition and alterations in survival signaling pathways","volume":"48","author":"Nitta","year":"2008","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib40","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1053\/j.gastro.2008.02.022","article-title":"Accumulation of hedgehog-responsive progenitors parallels alcoholic liver disease severity in mice and humans","volume":"134","author":"Jung","year":"2008","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2009.06.051_bib41","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","article-title":"Smad-dependent and Smad-independent pathways in TGF-\u03b2 family signalling","volume":"9","author":"Derynck","year":"2003","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2009.06.051_bib42","first-page":"68","article-title":"The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor \u03b2 in fetal rat hepatocytes","volume":"1","author":"Vald\u00e9s","year":"2002","journal-title":"Mol Cancer Res"},{"key":"10.1053\/j.gastro.2009.06.051_bib43","doi-asserted-by":"crossref","first-page":"22089","DOI":"10.1074\/jbc.M700998200","article-title":"Transforming growth factor-\u03b21 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro","volume":"282","author":"Kaimori","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1053\/j.gastro.2009.06.051_bib44","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/hep.510290347","article-title":"Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease","volume":"29","author":"Caldwell","year":"1999","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2009.06.051_bib45","doi-asserted-by":"crossref","first-page":"e2142","DOI":"10.1371\/journal.pone.0002142","article-title":"Functional Wnt signaling is increased in idiopathic pulmonary fibrosis","volume":"3","author":"Konigshoff","year":"2008","journal-title":"PLoS ONE"},{"key":"10.1053\/j.gastro.2009.06.051_bib46","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.devcel.2008.01.003","article-title":"Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye","volume":"14","author":"Fan","year":"2008","journal-title":"Dev Cell"},{"key":"10.1053\/j.gastro.2009.06.051_bib47","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1136\/gut.2008.148619","article-title":"The hedgehog pathway regulates remodelling responses to biliary obstruction in rats","volume":"57","author":"Omenetti","year":"2008","journal-title":"Gut"},{"key":"10.1053\/j.gastro.2009.06.051_fr1","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/labinvest.3700689","article-title":"Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice","volume":"87","author":"Fleig","year":"2007","journal-title":"Lab Invest"},{"key":"10.1053\/j.gastro.2009.06.051_fr2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jhep.2007.07.032","article-title":"Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells","volume":"48","author":"Yang","year":"2008","journal-title":"J Hepatol"}],"container-title":["Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508509011366?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508509011366?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T14:53:08Z","timestamp":1758034388000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508509011366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,10]]}},"alternative-id":["S0016508509011366"],"URL":"https:\/\/doi.org\/10.1053\/j.gastro.2009.06.051","relation":{},"ISSN":["0016-5085"],"issn-type":[{"value":"0016-5085","type":"print"}],"subject":[],"published":{"date-parts":[[2009,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hedgehog-Mediated Epithelial-to-Mesenchymal Transition and Fibrogenic Repair in Nonalcoholic Fatty Liver Disease","name":"articletitle","label":"Article Title"},{"value":"Gastroenterology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1053\/j.gastro.2009.06.051","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}