A red wine polyphenolic extract reduces the activation phenotype of cultured human liver myofibroblasts.
OBJECTIVE
To test the effect of a standardized red wine polyphenolic extract (RWPE) on the phenotype of human liver myofibroblasts in culture.


METHODS
Human myofibroblasts grown from liver explants were used in this study. Cell proliferation was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Signaling events were analyzed by western blot with phospho-specific antibodies. Matrix-metalloproteinase activity was measured with gel zymography.


RESULTS
We found that cell proliferation was dose-dependently decreased by up to 90% by RWPE while cell viability was not affected. Exposure to RWPE also greatly decreased the phosphorylation of ERK1/ERK2 and Akt in response to stimulation by the mitogenic factor platelet-derived growth factor BB (PDGF-BB). Finally, RWPE affected extracellular matrix remodeling by decreasing the secretion by myofibroblasts of matrix-metalloproteinase-2 and of tissue inhibitor of matrix-metalloproteinases-1.


CONCLUSIONS
Altogether, RWPE decreases the activation state of liver myofibroblasts. The identification of the active compounds in RWPE could offer new therapeutic strategies against liver fibrosis.
Neaud
Veronique
V
INSERM, U889, Universite Victor Segalen Bordeaux 2, Bordeaux 33076, France.
Rosenbaum
Jean
J
D000199:Actins / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D009210:Myofibrils / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010641:Phenotype; D010766:Phosphorylation; D059808:Polyphenols; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014920:Wine
D000199:Actins; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013778:Tetrazolium Salts; D013844:Thiazoles; D004247:DNA; C022616:thiazolyl blue