PMID- 16402030 OWN - NLM STAT- MEDLINE DCOM- 20060518 LR - 20230216 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 86 IP - 3 DP - 2006 Mar TI - Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices. PG - 275-85 AB - During cholestasis, bile acids accumulate in the liver, and induce cellular alterations. Cholestasis is a major cause of liver fibrosis. We have used precision-cut liver slices (PCLS) in culture to investigate the effects of bile acids on hepatic cells. Rat PCLS were placed on an insert in a vial containing culture medium, and gently agitated on a roller platform. PCLS were treated with 100 microM taurolithocholate (TLC), taurodeoxycholate (TDC) or taurocholate (TC) for 24 or 48 h. PCLS viability was measured, and immunohistochemistry was performed with antibodies against active caspase 3, platelet-derived growth factor (PDGF) receptor-beta and ED-A fibronectin. TDC and TLC, two hydrophobic bile acids, induced hepatocyte necrosis and apoptosis, whereas TC, an hydrophilic bile acid, improved slice viability as compared with controls. Both TDC and TC induced biliary epithelial cell proliferation, together with portal fibroblast proliferation and activation, as shown by PDGF receptor-beta and ED-A fibronectin expression. TLC induced biliary epithelial cell apoptosis. Our results indicate that individual bile acids induce cell type-specific effects in a complex liver microenvironment. The fact that PCLS support biliary epithelial cell and portal fibroblast proliferation will make this model very useful for the study of the mechanisms involved in portal fibrosis. FAU - Clouzeau-Girard, Haude AU - Clouzeau-Girard H AD - INSERM E0362, Universite Victor Segalen Bordeaux 2, Bordeaux, France. FAU - Guyot, Christelle AU - Guyot C FAU - Combe, Chantal AU - Combe C FAU - Moronvalle-Halley, Valerie AU - Moronvalle-Halley V FAU - Housset, Chantal AU - Housset C FAU - Lamireau, Thierry AU - Lamireau T FAU - Rosenbaum, Jean AU - Rosenbaum J FAU - Desmouliere, Alexis AU - Desmouliere A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Cholagogues and Choleretics) RN - 0 (Fibronectins) RN - 5E090O0G3Z (Taurocholic Acid) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Bile Ducts, Intrahepatic/*drug effects/pathology MH - Cell Proliferation/drug effects MH - Cholagogues and Choleretics/*toxicity MH - Epithelial Cells/*drug effects/pathology MH - Fibroblasts/*drug effects/pathology MH - Fibronectins/metabolism MH - Image Processing, Computer-Assisted MH - Liver/*drug effects/metabolism/pathology MH - Male MH - Necrosis MH - Portal System/drug effects/pathology MH - Rats MH - Rats, Wistar MH - Receptor, Platelet-Derived Growth Factor beta/metabolism MH - Taurocholic Acid/*toxicity EDAT- 2006/01/13 09:00 MHDA- 2006/05/19 09:00 CRDT- 2006/01/13 09:00 PHST- 2006/01/13 09:00 [pubmed] PHST- 2006/05/19 09:00 [medline] PHST- 2006/01/13 09:00 [entrez] AID - S0023-6837(22)60006-0 [pii] AID - 10.1038/labinvest.3700386 [doi] PST - ppublish SO - Lab Invest. 2006 Mar;86(3):275-85. doi: 10.1038/labinvest.3700386.