PMID- 17069927 OWN - NLM STAT- MEDLINE DCOM- 20070307 LR - 20141120 IS - 0168-8278 (Print) IS - 0168-8278 (Linking) VI - 46 IP - 1 DP - 2007 Jan TI - Fibrogenic cell fate during fibrotic tissue remodelling observed in rat and human cultured liver slices. PG - 142-50 AB - BACKGROUND/AIMS: Fibrotic liver remodelling was studied in culture of precision-cut liver slices (PCLS) derived from fibrotic liver. METHODS: Fibrosis was induced in rats by carbon tetrachloride (CCl4) treatment or bile duct ligation. Human fibrotic livers were also used. PCLS were cultured for 6, 24, 48, or 72 h, and the expression of alpha-smooth muscle (SM) actin, platelet-derived growth factor (PDGF) receptor-beta, and active caspase 3 was studied by immunohistochemistry. RESULTS: Before culture, in CCl4-treated or bile duct ligated animals, fibrosis was observed around centrolobular veins, or in portal zones, respectively. In PCLS derived from CCl4-treated animals, alpha-SM actin expression disappeared after 24h in culture while PDGF receptor-beta expression decreased progressively after 48 h. These changes were observed in absence of massive apoptosis. In PCLS derived from bile duct ligated animals, both alpha-SM actin and PDGF receptor-beta expression decreased after 48 h in culture with a massive apoptosis. In PCLS derived from human fibrotic livers, alpha-SM actin expression was dramatically reduced after 48 h in culture. CONCLUSIONS: After CCl4 treatment, a proportion of myofibroblasts derived from hepatic stellate cells seems to dedifferentiate while in bile duct ligation model, myofibroblasts derived from portal fibroblasts disappear by apoptosis, underlining the relevance of this model to evaluate the mechanisms involved in fibrotic liver remodelling. FAU - Guyot, Christelle AU - Guyot C AD - INSERM, E0362, Universite Victor Segalen Bordeaux 2, Bordeaux F-33076, France. FAU - Combe, Chantal AU - Combe C 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 - 20061004 PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 0 (Actins) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (platelet-derived growth factor A) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Actins/metabolism MH - Aged MH - Animals MH - Carbon Tetrachloride/toxicity MH - Extracellular Matrix/metabolism/pathology MH - Female MH - Humans MH - Liver Cirrhosis/etiology/metabolism/*pathology MH - Male MH - Microscopy, Electron MH - Middle Aged MH - Phenotype MH - Platelet-Derived Growth Factor/metabolism MH - Rats MH - Rats, Wistar MH - Tissue Culture Techniques/methods EDAT- 2006/10/31 09:00 MHDA- 2007/03/08 09:00 CRDT- 2006/10/31 09:00 PHST- 2006/03/18 00:00 [received] PHST- 2006/08/24 00:00 [revised] PHST- 2006/08/27 00:00 [accepted] PHST- 2006/10/31 09:00 [pubmed] PHST- 2007/03/08 09:00 [medline] PHST- 2006/10/31 09:00 [entrez] AID - S0168-8278(06)00498-3 [pii] AID - 10.1016/j.jhep.2006.08.013 [doi] PST - ppublish SO - J Hepatol. 2007 Jan;46(1):142-50. doi: 10.1016/j.jhep.2006.08.013. Epub 2006 Oct 4.