Deactivation of cultured human liver myofibroblasts by Trans‐resveratrol, a grapevine‐derived polyphenol
Deactivation of cultured human liver myofibroblasts by Trans‐resveratrol, a grapevine‐derived polyphenol
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DOI：
10.1053/he.2000.5848
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发表时间：
2000-04
期刊：
影响因子：
13.5
通讯作者：
S. Godichaud;S. Krisa;B. Couronné;L. Dubuisson;J. Mérillon;A. Desmoulière;J. Rosenbaum
中科院分区：
文献类型：
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作者：
S. Godichaud;S. Krisa;B. Couronné;L. Dubuisson;J. Mérillon;A. Desmoulière;J. Rosenbaum
肝肌成纤维细胞是肝纤维化和癌症进展的主要参与者。人们对可能使这些细胞失活的药物有很大的兴趣。许多研究表明，葡萄藤衍生的多酚，反式白藜芦醇和其他芪类化合物在某些疾病中具有治疗潜力。在这项工作中，我们研究了葡萄藤多酚对培养的人肝肌成纤维细胞的影响。我们已经证明，反式白藜芦醇深刻影响肌成纤维细胞表型。反式白藜芦醇诱导形态学改变。它以剂量依赖性方式显著降低肌成纤维细胞的增殖。反式白藜芦醇还降低了α平滑肌肌动蛋白（α SMA）的表达，而不影响波形蛋白或β细胞质肌动蛋白的表达。在单层创伤试验中，它降低了肌成纤维细胞迁移。我们还发现，反式白藜芦醇抑制I型胶原的信使RNA（mRNA）表达。最后，它减少了基质金属蛋白酶2（MMP-2）的分泌。我们得出结论，反式白藜芦醇可以使人肝肌成纤维细胞失活。在本研究的第二部分中，我们已经证明，无论是反式白藜芦醇苷（糖基化类似物）还是反式白藜芦醇（羟基化类似物）都不能再现反式白藜芦醇对肝肌成纤维细胞的作用。我们最终发现，尽管反式白藜芦醇降低了皮肤成纤维细胞和血管平滑肌细胞的增殖，但它并不影响α-SMA的表达，这表明了一些细胞特异性。
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.