PMID- 17431675 OWN - NLM STAT- MEDLINE DCOM- 20070828 LR - 20191210 IS - 0945-6317 (Print) IS - 0945-6317 (Linking) VI - 450 IP - 5 DP - 2007 May TI - Specific activation of the different fibrogenic cells in rat cultured liver slices mimicking in vivo situations. PG - 503-12 AB - Due to the loss of cell-cell and cell-matrix interactions, cell culture models poorly mimic the in vivo situation. Therefore, we tested the applicability of precision-cut liver slices (PCLS) to study the early activation of the two main liver fibrogenic cell subpopulations: hepatic stellate cells (HSC) and portal fibroblasts (PF). PCLS were treated with thioacetamide or acetaminophen to induce HSC activation. In PCLS culture, both were able to trigger centrolobular lesion and HSC activation as observed in vivo. However, thioacetamide also presented a toxic effect on portal tract cells. In this PCLS model of centrolobular lesion, the antioxidant N-acetylcysteine was able to prevent acetaminophen-induced injury. To induce a specific activation of PF, PCLS were treated with epidermal growth factor or beta-oestradiol. As in vivo, epidermal growth factor and beta-oestradiol induced bile duct epithelial cell proliferation accompanied by PF activation; however, beta-oestradiol also triggers sinusoidal cell proliferation. We demonstrated that treatments usually used in vivo to induce liver fibrosis allow, in cultured PCLS, the specific activation of the two main liver fibrogenic cell subpopulations, making this model very useful to study the mechanisms involved in early fibrogenic cell activation. FAU - Guyot, Christelle AU - Guyot C AD - INSERM, E362, Universite Victor Segalen Bordeaux 2, Bordeaux, 33076, France. FAU - Combe, Chantal AU - Combe C FAU - Clouzeau-Girard, Haude AU - Clouzeau-Girard H FAU - Moronvalle-Halley, Valerie AU - Moronvalle-Halley V FAU - Desmouliere, Alexis AU - Desmouliere A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20070313 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (Antioxidants) RN - 075T165X8M (Thioacetamide) RN - 362O9ITL9D (Acetaminophen) RN - 4TI98Z838E (Estradiol) RN - 62229-50-9 (Epidermal Growth Factor) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetaminophen/toxicity MH - Acetylcysteine/pharmacology MH - Animal Use Alternatives MH - Animals MH - Antioxidants/pharmacology MH - Bile Ducts, Intrahepatic/drug effects/pathology MH - Cell Survival/drug effects MH - *Disease Models, Animal MH - Drug Antagonism MH - Epidermal Growth Factor/pharmacology MH - Estradiol/pharmacology MH - Fibroblasts/drug effects/metabolism/*pathology MH - Hepatocytes/drug effects/pathology MH - Kupffer Cells/drug effects/metabolism/*pathology MH - Liver/drug effects/metabolism/*pathology MH - Liver Cirrhosis/chemically induced/pathology MH - Male MH - Necrosis MH - Organ Culture Techniques MH - Portal System/drug effects/metabolism/pathology MH - Rats MH - Rats, Wistar MH - Thioacetamide/toxicity EDAT- 2007/04/14 09:00 MHDA- 2007/08/29 09:00 CRDT- 2007/04/14 09:00 PHST- 2006/12/12 00:00 [received] PHST- 2007/02/12 00:00 [accepted] PHST- 2007/02/06 00:00 [revised] PHST- 2007/04/14 09:00 [pubmed] PHST- 2007/08/29 09:00 [medline] PHST- 2007/04/14 09:00 [entrez] AID - 10.1007/s00428-007-0390-y [doi] PST - ppublish SO - Virchows Arch. 2007 May;450(5):503-12. doi: 10.1007/s00428-007-0390-y. Epub 2007 Mar 13.