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紫檀芪通过调节丝裂原活化蛋白激酶(MAPK)信号通路抑制血管平滑肌细胞迁移和基质金属蛋白酶-2

Pterostilbene Inhibits Vascular Smooth Muscle Cells Migration and Matrix Metalloproteinase-2 through Modulation of MAPK Pathway.

作者信息

Lin Hsing-Chun, Hsieh Ming-Ju, Peng Chiung-Huei, Yang Shun-Fa, Huang Chien-Ning

机构信息

Inst. of Medicine, Chung Shan Medical Univ, Taichung, Taiwan.

School of Nutrition, Chung Shan Medical Univ, Taichung, Taiwan.

出版信息

J Food Sci. 2015 Oct;80(10):H2331-5. doi: 10.1111/1750-3841.13002. Epub 2015 Sep 26.

Abstract

UNLABELLED

Smooth muscle cells (SMCs) migration and matrix metalloproteinase-2 (MMP-2) activation are main roles in atherosclerosis. Pterostilbene (trans-3, 5-dimethoxy-4-hydroxystilbene) is known to have various pharmacologic effects such as anti-inflammatory and anticarcinogenic properties. The present study aimed to investigate the anti-atheroscleroic property of pterostilbene in the rat smooth muscle cell (SMC) A7r9 cell lines and the underlying mechanisms. In this study, pterostilbene treatment significantly inhibited migration/invasion capacities of in A7r9 cell. Pterostilbene was also found to significantly decreased MMP-2 activity and expression by gelatin zymography and western blot assay in SMC. In the MAPK signaling pathway, western blot assay also indicated that pterostilbene up-regulated the phosphorylation of extracellular-signal-regulated kinase (Erk)1/2. Moreover, inhibition of Erk1/2 by specific inhibitors significantly abolished the pterostilbene-decreased expression of MMP-2 and migration/invasion capacities. These findings suggest that pterostilbene inhibited SMC migration and that MMP-2 activation could be mediated via Erk1/2 phosphorylation. It is further possible that pterostilbene could play a novel role in the treatment of atherosclerosis.

PRACTICAL APPLICATION

Pterostilbene is a plant polyphenol compound that is principally found in blueberries. In this study, we found that pterostilbene could inhibit SMCs migration via down-regulation of MMP-2. Particularly, expression of MMP-2 was found to be strongly associated with the phosphorylation of Erk1/2.

摘要

未标记

平滑肌细胞(SMC)迁移和基质金属蛋白酶-2(MMP-2)激活是动脉粥样硬化的主要作用机制。已知紫檀芪(反式-3,5-二甲氧基-4-羟基芪)具有多种药理作用,如抗炎和抗癌特性。本研究旨在探讨紫檀芪在大鼠平滑肌细胞(SMC)A7r9细胞系中的抗动脉粥样硬化特性及其潜在机制。在本研究中,紫檀芪处理显著抑制了A7r9细胞的迁移/侵袭能力。通过明胶酶谱法和蛋白质免疫印迹分析还发现,紫檀芪可显著降低SMC中MMP-2的活性和表达。在丝裂原活化蛋白激酶(MAPK)信号通路中,蛋白质免疫印迹分析还表明,紫檀芪上调了细胞外信号调节激酶(Erk)1/2的磷酸化水平。此外,用特异性抑制剂抑制Erk1/2可显著消除紫檀芪降低的MMP-2表达及迁移/侵袭能力。这些发现表明,紫檀芪抑制了SMC迁移,且MMP-2激活可能通过Erk1/2磷酸化介导。紫檀芪进一步可能在动脉粥样硬化治疗中发挥新作用。

实际应用

紫檀芪是一种主要存在于蓝莓中的植物多酚化合物。在本研究中,我们发现紫檀芪可通过下调MMP-2来抑制SMC迁移。特别地,发现MMP-2的表达与Erk1/2的磷酸化密切相关。

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