Resveratrol inhibits BMP-4-stimulated VEGF synthesis in osteoblasts: Suppression of S6 kinase
Resveratrol inhibits BMP-4-stimulated VEGF synthesis in osteoblasts: Suppression of S6 kinase
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DOI：
10.3892/ijmm.2014.1626
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发表时间：
2014-04-01
影响因子：
5.4
通讯作者：
Tokuda, Haruhiko
中科院分区：
文献类型：
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作者：
Kondo, Akira;Otsuka, Takanobu;Tokuda, Haruhiko
白藜芦醇是众所周知的天然多酚，大量存在于红葡萄酒中。我们以前报道，骨形态发生蛋白-4（BMP-4）通过p70 S6激酶刺激成骨样MC3T3-E1细胞中血管内皮生长因子（VEGF）的合成。在本研究中，我们研究了白藜芦醇对BMP-4刺激的MC3T3-E1细胞VEGF合成的影响。白藜芦醇显着抑制BMP-4刺激的释放和VEGF mRNA的表达水平。SRT 1720是SIRT 1的激活剂，其效力大于白藜芦醇，也减少了VEGF的释放和mRNA水平。白藜芦醇和SRT 1720均显著减弱BMP-4诱导的p70 S6激酶磷酸化，而不影响BMP-4诱导的Smad1/5/8磷酸化。这些研究结果强烈表明，白藜芦醇通过抑制成骨细胞中p70 S6激酶的活化来减弱BMP-4刺激的VEGF合成，并且抑制作用至少部分由SIRT1活化介导。
Resveratrol is well known as a natural polyphenol abundantly found in red wine. We previously reported that bone morphogenetic protein-4 (BMP-4) stimulates vascular endothelial growth factor (VEGF) synthesis via p70 S6 kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of resveratrol on the BMP-4-stimulated VEGF synthesis in MC3T3-E1 cells. Resveratrol significantly suppressed BMP-4-stimulated release and expression levels of VEGF mRNA. SRT1720, an activator of SIRT1 with potencies greater than resveratrol, also reduced VEGF release and the mRNA levels. Both resveratrol and SRT1720 markedly attenuated the BMP-4-induced phosphorylation of p70 S6 kinase without affecting the BMP-4-induced phosphorylation of Smad1/5/8. These findings strongly suggest that resveratrol attenuates BMP-4-stimulated VEGF synthesis through suppression of the activation of p70 S6 kinase in osteoblasts, and that the inhibitory effect is mediated at least in part by SIRT1 activation.