title: Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers.
abstract: 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.
authors.affiliation: Laboratory of Cell Pharmacology, Herestraat 49, B-3000 Leuven, Belgium . david.cassiman@med.kuleuven.ac.be
authors.forename: David
authors.initials: D
authors.lastname: Cassiman
authors.forename: Louis
authors.initials: L
authors.lastname: Libbrecht
authors.forename: Valeer
authors.initials: V
authors.lastname: Desmet
authors.forename: Carl
authors.initials: C
authors.lastname: Denef
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
mesh_terms: 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
chemical_list: D000199:Actins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; C013090:ligatin; D002251:Carbon Tetrachloride