{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:55:59Z","timestamp":1791323759998,"version":"4.3.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2010,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>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 \u03b2-galactosidase (\u03b2-gal), albumin Cre, and collagen \u03b11(I) green fluorescent protein (GFP), in which hepatocyte-derived cells are permanently labeled by \u03b2-gal and type I collagen-expressing cells are labeled by GFP. We induced liver fibrosis by repetitive carbon tetrachloride (CCl4) injections. Liver sections and isolated cells were evaluated for GFP and \u03b2-gal as well as expression of \u03b1-smooth muscle actin (\u03b1-SMA) and fibroblast-specific protein 1 (FSP-1). Upon stimulation with transforming growth factor \u03b2-1, cultured hepatocytes isolated from untreated liver expressed both GFP and \u03b2-gal with a fibroblast-like morphological change but lacked expression of other mesenchymal markers. Cells from CCl4-treated livers never showed double-positivity for GFP and \u03b2-gal. All \u03b2-gal-positive cells exhibited abundant cytoplasm, a typical morphology of hepatocytes, and expressed none of the mesenchymal markers including \u03b1-SMA, FSP-1, desmin, and vimentin. In liver sections of CCl4-treated mice, GFP-positive areas were coincident with fibrotic septa and never overlapped X-gal-positive areas.<\/jats:bold>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      <jats:bold>Type I collagen-producing cells do not originate from hepatocytes. Hepatocytes<\/jats:bold>\n                      <jats:bold>in vivo<\/jats:bold>\n                      <jats:bold>neither acquire mesenchymal marker expression nor exhibit a morphological change clearly distinguishable from normal hepatocytes. Our results strongly challenge the concept that hepatocytes<\/jats:bold>\n                      <jats:bold>in vivo<\/jats:bold>\n                      <jats:bold>acquire a mesenchymal phenotype through EMT to produce the ECM in liver fibrosis. (Hepatology 2009.)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.23368","type":"journal-article","created":{"date-parts":[[2009,10,13]],"date-time":"2009-10-13T20:33:11Z","timestamp":1255465991000},"page":"1027-1036","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":297,"title":["Hepatocytes Do Not Undergo Epithelial-Mesenchymal Transition in Liver Fibrosis in Mice"],"prefix":"10.1097","volume":"51","author":[{"given":"Kojiro","family":"Taura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouichi","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Iwaisako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph 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