{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Taura K"],"funding":["NIDDK NIH HHS","NIGMS NIH HHS"],"pagination":["1027-36"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2906231"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["51(3)"],"pubmed_abstract":["<h4>Unlabelled</h4>The origin of fibrogenic cells in liver fibrosis remains controversial. We assessed the emerging concept that hepatocytes contribute to production of extracellular matrix (ECM) in liver fibrosis through epithelial-mesenchymal transition (EMT). We bred triple transgenic mice expressing ROSA26 stop beta-galactosidase (beta-gal), albumin Cre, and collagen alpha1(I) green fluorescent protein (GFP), in which hepatocyte-derived cells are permanently labeled by beta-gal and type I collagen-expressing cells are labeled by GFP. We induced liver fibrosis by repetitive carbon tetrachloride (CCl(4)) injections. Liver sections and isolated cells were evaluated for GFP and beta-gal as well as expression of alpha-smooth muscle actin (alpha-SMA) and fibroblast-specific protein 1 (FSP-1). Upon stimulation with transforming growth factor beta-1, cultured hepatocytes isolated from untreated liver expressed both GFP and beta-gal with a fibroblast-like morphological change but lacked expression of other mesenchymal markers. Cells from CCl(4)-treated livers never showed double-positivity for GFP and beta-gal. All beta-gal-positive cells exhibited abundant cytoplasm, a typical morphology of hepatocytes, and expressed none of the mesenchymal markers including alpha-SMA, FSP-1, desmin, and vimentin. In liver sections of CCl(4)-treated mice, GFP-positive areas were coincident with fibrotic septa and never overlapped X-gal-positive areas.<h4>Conclusion</h4>Type I collagen-producing cells do not originate from hepatocytes. Hepatocytes in vivo neither acquire mesenchymal marker expression nor exhibit a morphological change clearly distinguishable from normal hepatocytes. Our results strongly challenge the concept that hepatocytes in vivo acquire a mesenchymal phenotype through EMT to produce the ECM in liver fibrosis."],"journal":["Hepatology (Baltimore, Md.)"],"pubmed_title":["Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice."],"pmcid":["PMC2906231"],"funding_grant_id":["R01 GM041804","R01 GM041804-23","R01GM041804","R01 DK048252","R01 DK048252-17"],"pubmed_authors":["Miura K","Osterreicher CH","Iwaisako K","Kodama Y","Taura K","Penz-Osterreicher M","Brenner DA"],"additional_accession":[]},"is_claimable":false,"name":"Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice.","description":"<h4>Unlabelled</h4>The origin of fibrogenic cells in liver fibrosis remains controversial. We assessed the emerging concept that hepatocytes contribute to production of extracellular matrix (ECM) in liver fibrosis through epithelial-mesenchymal transition (EMT). We bred triple transgenic mice expressing ROSA26 stop beta-galactosidase (beta-gal), albumin Cre, and collagen alpha1(I) green fluorescent protein (GFP), in which hepatocyte-derived cells are permanently labeled by beta-gal and type I collagen-expressing cells are labeled by GFP. We induced liver fibrosis by repetitive carbon tetrachloride (CCl(4)) injections. Liver sections and isolated cells were evaluated for GFP and beta-gal as well as expression of alpha-smooth muscle actin (alpha-SMA) and fibroblast-specific protein 1 (FSP-1). Upon stimulation with transforming growth factor beta-1, cultured hepatocytes isolated from untreated liver expressed both GFP and beta-gal with a fibroblast-like morphological change but lacked expression of other mesenchymal markers. Cells from CCl(4)-treated livers never showed double-positivity for GFP and beta-gal. All beta-gal-positive cells exhibited abundant cytoplasm, a typical morphology of hepatocytes, and expressed none of the mesenchymal markers including alpha-SMA, FSP-1, desmin, and vimentin. In liver sections of CCl(4)-treated mice, GFP-positive areas were coincident with fibrotic septa and never overlapped X-gal-positive areas.<h4>Conclusion</h4>Type I collagen-producing cells do not originate from hepatocytes. Hepatocytes in vivo neither acquire mesenchymal marker expression nor exhibit a morphological change clearly distinguishable from normal hepatocytes. Our results strongly challenge the concept that hepatocytes in vivo acquire a mesenchymal phenotype through EMT to produce the ECM in liver fibrosis.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Mar","modification":"2025-04-22T06:45:30.71Z","creation":"2019-03-27T00:32:32Z"},"accession":"S-EPMC2906231","cross_references":{"pubmed":["20052656"],"doi":["10.1002/hep.23368"]}}