Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices.
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.
Clouzeau-Girard
Haude
H
INSERM E0362, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Guyot
Christelle
C
Combe
Chantal
C
Moronvalle-Halley
Valérie
V
Housset
Chantal
C
Lamireau
Thierry
T
Rosenbaum
Jean
J
Desmoulière
Alexis
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D011168:Portal System / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013656:Taurocholic Acid / Q000633:toxicity*
D002756:Cholagogues and Choleretics; D005353:Fibronectins; D013656:Taurocholic Acid; D020797:Receptor, Platelet-Derived Growth Factor beta