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Deactivation of cultured human liver myofibroblasts by Trans -resveratrol, a grapevine-derived polyphenol

2000; Lippincott Williams & Wilkins; Volume: 31; Issue: 4 Linguagem: Inglês

10.1053/he.2000.5848

1527-3350

Sandrine Godichaud, Stéphanie Krisa, Baptiste Couronné, L Dubuisson, Jean‐Michel Mérillon, Alexis Desmoulière, Jean Rosenbaum,

Endoplasmic Reticulum Stress and Disease

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.