Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers.
OBJECTIVE
Hepatic stellate cells (HSC) are commonly considered the precursor population of septal myofibroblasts (MF) in cirrhosis. We studied the distribution and expression profile of mesenchymal (myo)fibroblast-like populations in fibrotic and cirrhotic liver, in an attempt to elucidate their possible interrelationships.


METHODS
Fibrotic/cirrhotic livers (from 22 human explants and from two rat models: carbon tetrachloride intoxication, bile duct-ligation) were studied by means of immunohistochemistry (single and double immunostaining) with antibodies raised against desmin, alpha-smooth muscle actin (alpha SMA), glial fibrillary acidic protein (GFAP), neural-cell adhesion molecule (N-CAM), synaptophysin, neurotrophins, neurotrophin receptors and alpha B-crystallin (ABCRYS).


RESULTS
Septal MF showed the same expression profile as portal MF, in human and rat, being alpha SMA/ABCRYS/brain-derived nerve growth factor/GFAP-expression, with additional N-CAM- and desmin-expression in rat portal/septal MF. Perisinusoidally located HSC stained with all tested markers, MF at the septal/parenchymal interface showed an expression profile, intermediate between the profiles of HSC and portal/septal MF.


CONCLUSIONS
In advanced fibrosis and in cirrhosis, regardless of cause or species, three distinct mesenchymal (myo)fibroblast-like liver cell subpopulations can be discerned: portal/septal MF, interface MF and perisinusoidally located HSC. The fact that septal MF share more characteristics with portal MF than with HSC might suggest descent.
Cassiman
David
D
Laboratory of Cell Pharmacology, Herestraat 49, B-3000 Leuven, Belgium . david.cassiman@med.kuleuven.ac.be
Libbrecht
Louis
L
Desmet
Valeer
V
Denef
Carl
C
Roskams
Tania
T
D000199:Actins / Q000032:analysis; D000818:Animals; D002251:Carbon Tetrachloride; D001651:Cholestasis, Extrahepatic; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D022781:Hepatocytes / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; C013090:ligatin; D002251:Carbon Tetrachloride