Deactivation of cultured human liver myofibroblasts by trans-resveratrol, a grapevine-derived polyphenol.
Liver myofibroblasts are major actors in the development of liver fibrosis and cancer progression. There is a large interest in drugs that might deactivate these cells. Many studies have shown that the grapevine-derived polyphenol, trans-resveratrol, and other stilbenes have therapeutic potential in some diseases. In this work, we have studied the effect of grapevine polyphenols on cultured human liver myofibroblasts. We have shown that trans-resveratrol profoundly affects myofibroblast phenotype. Trans-resveratrol induced morphological modifications. It markedly reduced proliferation of myofibroblasts in a dose-dependent manner. Trans-resveratrol also decreased the expression of alpha smooth muscle actin (alpha-SMA) without affecting vimentin or beta-cytoplasmic actin expression. It decreased myofibroblast migration in a monolayer wounding assay. We also showed that trans-resveratrol inhibited the messenger RNA (mRNA) expression of type I collagen. Finally, it decreased the secretion of matrix metalloproteinase 2 (MMP-2). We conclude that trans-resveratrol can deactivate human liver myofibroblasts. In the second part of this study, we have shown that neither trans-piceid (a glycosylated analog) nor trans-piceatannol (a hydroxylated analog) reproduces trans-resveratrol effects on liver myofibroblasts. We finally show that, although trans-resveratrol decreases the proliferation of skin fibroblast and vascular smooth muscle cells, it does not affect their expression of alpha-SMA, which indicates some cell specificity.
Godichaud
S
S
Groupe de Recherches pour l'Etude du Foie INSERM E9917, Faculté des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Krisa
S
S
Couronné
B
B
Dubuisson
L
L
Mérillon
J M
JM
Desmoulière
A
A
Rosenbaum
J
J
D000199:Actins / Q000032:analysis; D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000166:cytology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008854:Microscopy, Electron; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000077185:Resveratrol; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013267:Stilbenes / Q000494:pharmacology*
D000199:Actins; D000975:Antioxidants; D011347:Procollagen; D012333:RNA, Messenger; D013267:Stilbenes; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D000077185:Resveratrol