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 α smooth muscle actin (α‐SMA) without affecting vimentin or β‐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 α‐SMA, which indicates some cell specificity.