Reversal of activation of human myofibroblast-like cells by culture on a basement membrane-like substrate.
J Hepatol
; 37(2): 214-21, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12127426
ABSTRACT
BACKGROUND:
Liver injury transforms hepatic stellate cells into myofibroblast (MFB)-like cells. With recovery from injury, MFBs undergo apoptosis, but it is unknown whether they can also revert to quiescence.AIM:
To determine whether human (h)MFBs become quiescent if cultured on a basement membrane-like substrate (Matrigel).METHODS:
hMFBs obtained from cirrhotic liver were re-cultured on plastic or Matrigel. Expression of genes of collagen metabolism was assayed before and after transforming growth factor beta (TGFbeta) and Oncostatin M (OSM) stimulation.RESULTS:
hMFBs had typical MFB-like morphology, with abundant alpha-smooth muscle actin (SMA) but no cytoplasmic lipid droplets. hMFBs re-cultured on Matrigel reverted to alphaSMA-negative, lipid droplet-positive quiescent morphology. alphaSMA, collagen alpha1(1) (COL1A1) and collagen alpha2(1) (COL1A2) messages were upregulated in hMFBs cultured on plastic, but suppressed by Matrigel. The opposite was true for metalloproteinase-1 mRNA. OSM but not TGFbeta reduced alphaSMA mRNA by 30% while TGFbeta but not OSM upregulated COL1A1 mRNA by 48%, in hMFBs on plastic. TGFbeta and OSM stimulated COL1A1 gene expression in Matrigel by 50 and 60%, respectively.CONCLUSIONS:
Matrigel culture de-activates hMFBs yet collagen gene expression still responds to fibrogenic cytokines. The responses of hMFB gene expression to TGFbeta and OSM, are regulated differently by the extracellular matrix.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Técnicas de Cultura de Células
/
Hepatócitos
/
Colágeno Tipo I
/
Fibroblastos
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article