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

Authors

  • Sandrine Godichaud,

    1. Groupe de Recherches pour l'Etude du Foie INSERM E9917, Université Victor Segalen Bordeaux 2, Bordeaux, France
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  • Stéphanie Krisa,

    1. Laboratoire de Mycologie et Biologie Végétale, Faculté des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, Bordeaux, France
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  • Baptiste Couronné,

    1. Groupe de Recherches pour l'Etude du Foie INSERM E9917, Université Victor Segalen Bordeaux 2, Bordeaux, France
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  • Liliane Dubuisson,

    1. Groupe de Recherches pour l'Etude du Foie INSERM E9917, Université Victor Segalen Bordeaux 2, Bordeaux, France
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  • Jean-Michel Mérillon,

    1. Laboratoire de Mycologie et Biologie Végétale, Faculté des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, Bordeaux, France
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  • Alexis Desmoulière,

    1. Groupe de Recherches pour l'Etude du Foie INSERM E9917, Université Victor Segalen Bordeaux 2, Bordeaux, France
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  • Jean Rosenbaum

    Corresponding author
    1. Groupe de Recherches pour l'Etude du Foie INSERM E9917, Université Victor Segalen Bordeaux 2, Bordeaux, France
    • Groupe de Recherches pour l'Etude du Foie INSERM E9917, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. fax: (33)-5-56514077
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Abstract

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.

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