Fibrogenic cell phenotype modifications during remodelling of normal and pathological human liver in cultured slices.
BACKGROUND
The debate concerning the potential remodelling and/or reversibility of cirrhotic lesions and biliary fibrosis is still open.


OBJECTIVE
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, α-smooth muscle (SM) actin was present only in the vessel walls. Platelet-derived growth factor (PDGF) receptor-β 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, α-SM actin, PDGF receptor-β and Thy-1 were expressed in septa; after culture, α-SM actin expression disappeared but the expression of the PDGF receptor-β and Thy-1 was maintained. In cholestatic liver specimens, α-SM actin, PDGF receptor-β 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-β 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.
Guyot
Christelle
C
INSERM U889 and Université Victor Segalen Bordeaux 2, Bordeaux, France.
Lepreux
Sébastien
S
Combe
Chantal
C
Sarrazy
Vincent
V
Billet
Fabrice
F
Balabaud
Charles
C
Bioulac-Sage
Paulette
P
Desmoulière
Alexis
A
D000199:Actins / Q000378:metabolism; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002780:Cholestasis, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques
D000199:Actins; D018952:Antigens, CD34; D015415:Biomarkers; D053539:Keratin-19; D019394:Ki-67 Antigen; D018800:Thy-1 Antigens; D020797:Receptor, Platelet-Derived Growth Factor beta