PMID- 20846345 OWN - NLM STAT- MEDLINE DCOM- 20110211 LR - 20210102 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 30 IP - 10 DP - 2010 Nov TI - Fibrogenic cell phenotype modifications during remodelling of normal and pathological human liver in cultured slices. PG - 1529-40 LID - 10.1111/j.1478-3231.2010.02342.x [doi] AB - BACKGROUND: The debate concerning the potential remodelling and/or reversibility of cirrhotic lesions and biliary fibrosis is still open. AIMS/METHODS: In this work, we have used the precision-cut liver slice (PCLS) model, which maintains cell-cell and cell-matrix interactions to study, by immunohistochemistry, the behaviour of the different fibrogenic cells, i.e. hepatic stellate cells (HSC) and portal fibroblasts, in cultured (for 1 week) PCLS derived from normal and fibrotic human livers. RESULTS: In normal liver, before and after culture, alpha-smooth muscle (SM) actin was present only in the vessel walls. Platelet-derived growth factor (PDGF) receptor-beta was expressed before and after culture by portal fibroblasts, and appeared after culture in HSC. Before culture, CD 34 was not expressed in parenchyma, but appeared after culture in sinusoidal endothelial cells. In cirrhotic lesions, before culture, alpha-SM actin, PDGF receptor-beta and Thy-1 were expressed in septa; after culture, alpha-SM actin expression disappeared but the expression of the PDGF receptor-beta and Thy-1 was maintained. In cholestatic liver specimens, alpha-SM actin, PDGF receptor-beta and Thy-1 expression, which was present before culture in enlarged portal areas, disappeared after culture, and apoptosis was detected. In the parenchyma of both cirrhotic and cholestatic livers, the expression of the PDGF receptor-beta and of CD 34, which was not observed before culture, was present in HSC and sinusoidal endothelial cells, respectively, after culture. CONCLUSIONS: These results indicate that during remodelling of pathological tissues in cultured liver slices, the myofibroblastic cells derived from HSC or from portal fibroblasts show different behaviours, suggesting different mechanisms of activation/deactivation. CI - (c) 2010 John Wiley & Sons A/S. FAU - Guyot, Christelle AU - Guyot C AD - INSERM U889 and Universite Victor Segalen Bordeaux 2, Bordeaux, France. FAU - Lepreux, Sebastien AU - Lepreux S FAU - Combe, Chantal AU - Combe C FAU - Sarrazy, Vincent AU - Sarrazy V FAU - Billet, Fabrice AU - Billet F FAU - Balabaud, Charles AU - Balabaud C FAU - Bioulac-Sage, Paulette AU - Bioulac-Sage P FAU - Desmouliere, Alexis AU - Desmouliere A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100916 PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (Actins) RN - 0 (Antigens, CD34) RN - 0 (Biomarkers) RN - 0 (Keratin-19) RN - 0 (Ki-67 Antigen) RN - 0 (Thy-1 Antigens) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) SB - IM MH - Actins/metabolism MH - Aged MH - Antigens, CD34/metabolism MH - Apoptosis MH - Bile Ducts, Intrahepatic/metabolism/pathology MH - Biomarkers/metabolism MH - Cell Proliferation MH - *Cell Transdifferentiation MH - Cholestasis, Intrahepatic/metabolism/*pathology MH - Endothelial Cells/metabolism/pathology MH - Female MH - Fibroblasts/metabolism/*pathology MH - Hepatic Stellate Cells/metabolism/*pathology MH - Humans MH - Immunohistochemistry MH - Keratin-19/metabolism MH - Ki-67 Antigen/metabolism MH - Liver/metabolism/*pathology MH - Liver Cirrhosis/metabolism/*pathology MH - Male MH - Middle Aged MH - Myofibroblasts/metabolism/pathology MH - Phenotype MH - Receptor, Platelet-Derived Growth Factor beta/metabolism MH - Thy-1 Antigens/metabolism MH - Time Factors MH - Tissue Culture Techniques EDAT- 2010/09/18 06:00 MHDA- 2011/02/12 06:00 CRDT- 2010/09/18 06:00 PHST- 2010/09/18 06:00 [entrez] PHST- 2010/09/18 06:00 [pubmed] PHST- 2011/02/12 06:00 [medline] AID - 10.1111/j.1478-3231.2010.02342.x [doi] PST - ppublish SO - Liver Int. 2010 Nov;30(10):1529-40. doi: 10.1111/j.1478-3231.2010.02342.x. Epub 2010 Sep 16.