{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:51:12Z","timestamp":1791093072475,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2314,"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":[[2009,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      In chronic liver injury, liver progenitor cells (LPCs) proliferate in the periportal area, migrate inside the lobule, and undergo further differentiation. This process is associated with extracellular matrix (ECM) remodeling. We analyzed LPC expansion and matrix accumulation in a choline-deficient, ethionine-supplemented (CDE) model of LPC proliferation. After day 3, CDE induced collagen deposits in the periportal area. Expansion of LPCs as assessed by increased number of cytokeratin 19 (CK19)-positive cells was first observed at day 7, while ECM accumulated 10 times more than in controls. Thereafter, LPCs and ECM increased in parallel. Furthermore, ECM not only accumulates prior to the increase in number of LPCs, but is also found in front of LPCs along the porto-venous gradient of lobular invasion. Double immunostaining revealed that LPCs are embedded in ECM at all times. Moreover, LPCs infiltrating the liver parenchyma are chaperoned by \u03b1-smooth muscle actin (\u03b1-SMA)\u2013positive cells. Gene expression analyses confirmed these observations. The expression of CK19, \u03b1-fetoprotein, E-cadherin, and CD49f messenger RNA (mRNA), largely overexpressed by LPCs, significantly increased between day 7 and day 10. By contrast, at day 3 there was a rapid burst in the expression of components of the ECM, collagen I and laminin, as well as in \u03b1-SMA and connective tissue growth factor expression.\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                      Our data demonstrate that, in a CDE model, ECM deposition and activation of matrix-producing cells occurred as an initial phase, prior to LPC expansion, and in front of LPCs along the porto-veinous gradient of lobular invasion. Those observations may reveal a fundamental role for the established hepatic microenvironment or niche during the process of activation and differentiation of liver progenitor cells. (Hepatology 2009.)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.22820","type":"journal-article","created":{"date-parts":[[2009,1,5]],"date-time":"2009-01-05T23:26:41Z","timestamp":1231198001000},"page":"1625-1635","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":144,"title":["Relation between liver progenitor cell expansion and extracellular matrix deposition in a CDE-induced murine model of chronic liver injury #"],"prefix":"10.1097","volume":"49","author":[{"given":"No\u00e9mi K. M.","family":"Van Hul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Abarca-Quinones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sempoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Horsmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle A.","family":"Leclercq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-26-20241201","first-page":"149","article-title":"Hepatic regenerationrevisiting the myth of Prometheus.","volume":"14","author":"AnkomaSey","year":"1999","journal-title":"News Physiol Sci"},{"key":"R2-26-20241201","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0925-4773(02)00338-6","article-title":"The role of hepatocytes and oval cells in liver regeneration and repopulation.","volume":"120","author":"Fausto","year":"2003","journal-title":"Mech Dev"},{"key":"R3-26-20241201","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1365-2184.1996.tb00982.x","article-title":"Pluripotential liver stem cells: facultative stem cells located in the biliary tree.","volume":"29","author":"Alison","year":"1996","journal-title":"Cell Prolif"},{"key":"R4-26-20241201","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3181\/00379727-204-43660","article-title":"Models for hepatic progenitor cell activation.","volume":"204","author":"Dabeva","year":"1993","journal-title":"Proc Soc Exp Biol Med"},{"key":"R5-26-20241201","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/j.1600-0463.2005.apm_386.x","article-title":"Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion.","volume":"113","author":"SantoniRugiu","year":"2005","journal-title":"APMIS"},{"key":"R6-26-20241201","first-page":"445","article-title":"Carcinoma of the liver in rats fed ethionine.","volume":"62","author":"Farber","year":"1956","journal-title":"AMA Arch Pathol"},{"key":"R7-26-20241201","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1096\/fasebj.10.11.8836038","article-title":"Hepatic stem cells in liver regeneration.","volume":"10","author":"Thorgeirsson","year":"1996","journal-title":"FASEB J"},{"key":"R8-26-20241201","first-page":"1207","article-title":"Expression of matrix proteinases during human intrahepatic bile duct development. A possible role in biliary cell migration.","volume":"147","author":"Terada","year":"1995","journal-title":"Am J Pathol"},{"key":"R9-26-20241201","first-page":"3439","article-title":"Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis in the rat.","volume":"50","author":"Evarts","year":"1990","journal-title":"Cancer Res"},{"key":"R10-26-20241201","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis.","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"R11-26-20241201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20071570","article-title":"Liver fibrosis.","volume":"411","author":"Wallace","year":"2008","journal-title":"Biochem J"},{"key":"R12-26-20241201","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.3748\/wjg.v10.i8.1208","article-title":"Hepatic progenitor cells in human liver cirrhosis: immunohistochemical, electron microscopic and immunofluorencence confocal microscopic findings.","volume":"10","author":"Xiao","year":"2004","journal-title":"World J Gastroenterol"},{"key":"R13-26-20241201","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":"R14-26-20241201","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.3748\/wjg.v12.i9.1443","article-title":"Ductular proliferation in liver tissues with severe chronic hepatitis B: an immunohistochemical study.","volume":"12","author":"Chen","year":"2006","journal-title":"World J Gastroenterol"},{"key":"R15-26-20241201","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0002-9440(10)65299-6","article-title":"Oval cell numbers in human chronic liver diseases are directly related to disease severity.","volume":"154","author":"Lowes","year":"1999","journal-title":"Am J Pathol"},{"key":"R16-26-20241201","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH700>3.0.CO;2-5","article-title":"Deep intralobular extension of human hepatic progenitor cells correlates with parenchymal inflammation in chronic viral hepatitis: can progenitor cells migrate?","volume":"192","author":"Libbrecht","year":"2000","journal-title":"J Pathol"},{"key":"R17-26-20241201","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/hep.20130","article-title":"Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers.","volume":"39","author":"Roskams","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R18-26-20241201","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1034\/j.1600-0676.2002.01622.x","article-title":"Immunohistochemical evidence for hepatic progenitor cells in liver diseases.","volume":"22","author":"Tan","year":"2002","journal-title":"Liver"},{"key":"R19-26-20241201","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1111\/j.1478-3231.2006.01306.x","article-title":"Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy: a clinicopathologic study.","volume":"26","author":"Tsamandas","year":"2006","journal-title":"Liver Int"},{"key":"R20-26-20241201","doi-asserted-by":"crossref","first-page":"6261","DOI":"10.3748\/wjg.v12.i39.6261","article-title":"Hepatic progenitor cells in human liver tumor development.","volume":"12","author":"Libbrecht","year":"2006","journal-title":"World J Gastroenterol"},{"key":"R21-26-20241201","first-page":"1554","article-title":"Production of hepatocellular carcinoma by oval cells: cell cycle expression of cmyc and p53 at different stages of oval cell transformation.","volume":"49","author":"Braun","year":"1989","journal-title":"Cancer Res"},{"key":"R22-26-20241201","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/hep.20650","article-title":"Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis.","volume":"41","author":"Clouston","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R23-26-20241201","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1055\/s-2004-815564","article-title":"Progenitor cells in diseased human liver.","volume":"23","author":"Roskams","year":"2003","journal-title":"Semin Liver Dis"},{"key":"R24-26-20241201","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":"R25-26-20241201","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jhep.2006.08.015","article-title":"Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALBc inbred strain of mice.","volume":"46","author":"Knight","year":"2007","journal-title":"J Hepatol"},{"key":"R26-26-20241201","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1053\/j.gastro.2005.03.081","article-title":"Role of connective tissue growth factor in oval cell response during liver regeneration after 2AAFPHx in rats.","volume":"128","author":"Pi","year":"2005","journal-title":"Gastroenterology"},{"key":"R27-26-20241201","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1016\/j.biocel.2007.06.008","article-title":"Isolation, culture and immortalisation of hepatic oval cells from adult mice fed a cholinedeficient, ethioninesupplemented diet.","volume":"39","author":"TirnitzParker","year":"2007","journal-title":"Int J Biochem Cell Biol"},{"key":"R28-26-20241201","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.2353\/ajpath.2007.070273","article-title":"Thy1 is expressed in hepatic myofibroblasts and not oval cells in stem cellmediated liver regeneration.","volume":"171","author":"Dezso","year":"2007","journal-title":"Am J Pathol"},{"key":"R29-26-20241201","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00441-007-0437-z","article-title":"Thy1 is an in vivo and in vitro marker of liver myofibroblasts.","volume":"329","author":"Dudas","year":"2007","journal-title":"Cell Tissue Res"},{"key":"R30-26-20241201","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/hep.22047","article-title":"Identification of adult hepatic progenitor cells capable of repopulating injured rat liver.","volume":"47","author":"Yovchev","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R31-26-20241201","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0002-9440(10)63810-2","article-title":"Hepatic microenvironment affects oval cell localization in albuminurokinasetype plasminogen activator transgenic mice.","volume":"162","author":"Braun","year":"2003","journal-title":"Am J Pathol"},{"key":"R32-26-20241201","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1053\/jhep.2001.26751","article-title":"A modified cholinedeficient, ethioninesupplemented diet protocol effectively induces oval cells in mouse liver.","volume":"34","author":"Akhurst","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R33-26-20241201","first-page":"105","article-title":"Peroxisome proliferatedactivated receptor gamma ligand, Pioglitazone, does not prevent hepatic fibrosis in mice.","volume":"19","author":"Da Silva Morais","year":"2007","journal-title":"Int J Mol Med"},{"key":"R34-26-20241201","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s10735-007-9098-1","article-title":"Ecadherin as a reliable cell surface marker for the identification of liver specific stem cells.","volume":"38","author":"Ueberham","year":"2007","journal-title":"J Mol Histol"},{"key":"R35-26-20241201","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1002\/hep.20180","article-title":"Thy1positive mesenchymal cells promote the maturation of CD49fpositive hepatic progenitor cells in the mouse fetal liver.","volume":"39","author":"Hoppo","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R36-26-20241201","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0002-9440(10)64565-8","article-title":"Liver damage using suicide genes. A model for oval cell activation.","volume":"157","author":"Bustos","year":"2000","journal-title":"Am J Pathol"},{"key":"R37-26-20241201","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/S0002-9440(10)64082-5","article-title":"Origin and structural evolution of the early proliferating oval cells in rat liver.","volume":"158","author":"Paku","year":"2001","journal-title":"Am J Pathol"},{"key":"R38-26-20241201","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF00870306","article-title":"Liver fibrosis.","volume":"21","author":"Pinzani","year":"1999","journal-title":"Springer Semin Immunopathol"},{"key":"R39-26-20241201","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00418-006-0204-3","article-title":"Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration.","volume":"126","author":"Koenig","year":"2006","journal-title":"Histochem Cell Biol"},{"key":"R40-26-20241201","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/hep.510270218","article-title":"Hepatic oval cells express the hematopoietic stem cell marker Thy1 in the rat.","volume":"27","author":"Petersen","year":"1998","journal-title":"HEPATOLOGY"},{"key":"R41-26-20241201","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0168-8278(02)00263-5","article-title":"Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic stellate cell research.","volume":"37","author":"Cassiman","year":"2002","journal-title":"J Hepatol"},{"key":"R42-26-20241201","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1634\/stemcells.2008-0115","article-title":"Fatemapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers.","volume":"26","author":"Yang","year":"2008","journal-title":"Stem Cells"},{"key":"R43-26-20241201","doi-asserted-by":"crossref","first-page":"G526","DOI":"10.1152\/ajpgi.00241.2006","article-title":"Two populations of Thy1positive mesenchymal cells regulate in vitro maturation of hepatic progenitor cells.","volume":"292","author":"Kamo","year":"2007","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R44-26-20241201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7696(06)59001-1","article-title":"Molecular mechanism of liver development and regeneration.","volume":"259","author":"Tanimizu","year":"2007","journal-title":"Int Rev Cytol"},{"key":"R45-26-20241201","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1073\/pnas.94.20.10663","article-title":"Strainspecific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses.","volume":"94","author":"Shi","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R46-26-20241201","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/hep.22218","article-title":"The hepatic stem cell niche: identification by labelretaining cell assay.","volume":"47","author":"Kuwahara","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R47-26-20241201","first-page":"397","article-title":"Morphometric and immunohistochemical characterization of human liver regeneration.","volume":"147","author":"Rubin","year":"1995","journal-title":"Am J Pathol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.22820","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200905000-00026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T08:44:10Z","timestamp":1733042650000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200905000-00026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2009]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.22820","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1164245.624948","asserted-by":"object"}]},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2009,5]]}}}