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首页> 外文期刊>Cellular Physiology and Biochemistry >Heat Shock Protein 70 Negatively Regulates TGF-?2-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts
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Heat Shock Protein 70 Negatively Regulates TGF-?2-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts

机译：热休克蛋白70通过成骨细胞中的p38 MAP激酶负调节TGF-β2刺激的VEGF合成。

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>Background/Aims: We previously demonstrated that transforming growth factor-?2 (TGF-?2) stimulates the synthesis of vascular endothelial growth factor (VEGF) through the activation of p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70) is a ubiquitously expressed molecular chaperone. In the present study, we investigated the involvement of HSP70 in the TGF-?2-stimulated VEGF synthesis and the underlying mechanism in these cells. Methods: Culture MC3T3-E1 cells were stimulated by TGF-?2. Released VEGF was measured using an ELISA assay. VEGF mRNA level was quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by Western blotting. Results: VER-155008 and YM-08, both of HSP70 inhibitors, significantly amplified the TGF-?2-stimulated VEGF release. In addition, the expression level of VEGF mRNA induced by TGF-?2 was enhanced by VER-155008. These inhibitors markedly strengthened the TGF-?2-induced phosphorylation of p38 MAP kinase. The TGF-?2-induced phosphorylation of p38 MAP kinase was amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by these inhibitors of the TGF-?2-induced VEGF release. Conclusion: These results strongly suggest that HSP70 acts as a negative regulator in the TGF-?2-stimulated VEGF synthesis in osteoblasts, and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP kinase.
机译：> 背景/目的： 我们先前证明，转化生长因子-α2（TGF-β2）通过促生长因子刺激血管内皮生长因子（VEGF）的合成。在成骨细胞样MC3T3-E1细胞中激活p38丝裂原活化蛋白（MAP）激酶。热休克蛋白70（HSP70）是一种普遍表达的分子伴侣。在本研究中，我们研究了HSP70参与TGF-β2刺激的VEGF合成及其在这些细胞中的潜在机制。 方法： 培养物通过TGF-β2刺激MC3T3-E1细胞。使用ELISA测定法测量释放的VEGF。通过RT-PCR定量VEGF mRNA水平。通过蛋白质印迹分析每种蛋白激酶的磷酸化。 结果： 两种HSP70抑制剂VER-155008和YM-08均显着扩增了TGF-β2刺激的VEGF释放。另外，VER-155008提高了TGF-β2诱导的VEGF mRNA的表达水平。这些抑制剂显着增强了TGF-β2诱导的p38 MAP激酶的磷酸化。在HSP70敲低的细胞中，TGF-β2诱导的p38 MAP激酶的磷酸化被放大。 SB203580，p38 MAP激酶的抑制剂，显着抑制了这些抑制剂对TGF-β2诱导的VEGF释放的扩增。 结论： 这些结果强烈表明，HSP70在成骨细胞中由TGF-β2刺激的VEGF合成中起负调节作用，并且HSP70的抑制作用在p38 MAP激酶上游的一个点。

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