Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts.
OBJECTIVE
Hepatic stellate cells (HSC) and rat liver myofibroblasts (rMF), two similar but not identical cell populations, play a major role during hepatic tissue repair.


METHODS
To identify marker proteins for the different fibroblastic cell populations, m-RNA-profiling technology was employed using c-DNAs prepared from HSC and rMF.


CONCLUSIONS
The extracellular matrix protein reelin was identified through its presence in HSC and absence in rMF derived samples. As confirmed by Northern blot analysis and by immunoprecipitation, reelin expression was present in similar amounts in resting and activated HSC and was not detectable in rMF. Therefore reelin is the only marker presently available to distinguish HSC at any stage of differentiation from rMF. Following a single CCl4 mediated liver injury, reelin specific mRNAs were induced early, were elevated up to 24 h following CCl4 dosage and were diminished afterwards. Hepatocytes and non-parenchymal liver cells located in the damaged areas were identified as the main cellular source of enhanced reelin expression. Although reelin expression was upregulated during liver injury, reelin deficient mice recovered completely suggesting either a more distinct role in tissue repair reactions or a case of redundancy through the action of related proteins.
Kobold
Dominik
D
Department of Internal Medicine, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.
Grundmann
Anka
A
Piscaglia
Fabio
F
Eisenbach
Christoph
C
Neubauer
Katrin
K
Steffgen
Jürgen
J
Ramadori
Giuliano
G
Knittel
Thomas
T
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology*; D066298:In Vitro Techniques; D008107:Liver Diseases / Q000503:physiopathology*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins; D051381:Rats; D017208:Rats, Wistar; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases