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 drags that might deact ivate these cells. Many studies have shown that the grapevine-derived polyp henol, trans-resveratrol, and other stilbenes have therapeutic potential in some diseases. In this work, we have studied the effect of grapevine polyp henols on cultured human liver myofibroblasts. We have shown that trans-res veratrol profoundly affects myofibroblast: phenotype. Trans-resveratrol ind uced morphological modifications. It markedly reduced proliferation of myof ibroblasts in a dose-dependent manner. Trans-resveratrol also decreased the expression of a 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 chat trans-resveratrol inhib ited the messenger RNA (mRNA) expression of type I collagen. Finally it dec reased the secretion of matrix metalloproteinase 2 (MMP-2). We conclude tha t trans-resveratrol can deactivate human liver myofibroblasts. In the secon d part of this study, we have shown that neither trans-piceid (a glycosylat ed analog) nor trans-piceatannol (a hydroxylated analog) reproduces trans-r esveratrol effects on liver myofibroblasts. We finally show that, although trans-resveratrol decreases the proliferation of skin fibroblast and vascul ar smooth muscle cells, it does not affect their expression of alpha-SMA, w hich indicates some cell specificity.