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Role of heat shock protein 27 in transforming growth factor-β-stimulated vascular endothelial growth factor release in osteoblasts

机译:热休克蛋白27在成骨细胞中转化生长因子-β刺激的血管内皮生长因子释放中的作用

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We have previously reported that transforming growth factor-β (TGF-β) stimulates heat shock protein?27 (HSP27) induction via p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase in osteoblast-like MC3T3-E1 cells, and that the release of vascular endothelial growth factor (VEGF) is induced by TGF-β in these cells. In the present study, we investigated the effect of HSP27 knockdown on the TGF-β-stimulated VEGF release in these cells. Gene silencing using short interfering RNA against HSP27 (HSP27-siRNA) significantly suppressed the TGF-β-induced VEGF release. Immunofluorescence microscopy also revealed that HSP27-siRNA suppressed the TGF-β-stimulated VEGF induction as well as the reduction of HSP27 induction in these cells. However, the mRNA expression of VEGF stimulated by TGF-β was not reduced even in cells transfected with HSP27-siRNA. These results strongly suggest that HSP27 induction is critical for TGF-β-induced VEGF release in osteoblasts.
机译:我们先前曾报道过转化生长因子-β(TGF-β)通过p44 / p42丝裂原活化蛋白(MAP)激酶,p38 MAP激酶和应激活化蛋白激酶/ c-刺激热休克蛋白?27(HSP27)诱导。在成骨细胞样MC3T3-E1细胞中存在Jun端激酶,并且TGF-β诱导了这些细胞中血管内皮生长因子(VEGF)的释放。在本研究中,我们研究了HSP27敲低对这些细胞中TGF-β刺激的VEGF释放的影响。使用针对HSP27的短干扰RNA(HSP27-siRNA)进行基因沉默可显着抑制TGF-β诱导的VEGF释放。免疫荧光显微镜检查还显示,在这些细胞中,HSP27-siRNA抑制了TGF-β刺激的VEGF诱导以及HSP27诱导的降低。然而,即使在用HSP27-siRNA转染的细胞中,TGF-β刺激的VEGF的mRNA表达也没有降低。这些结果强烈表明,HSP27诱导对于成骨细胞中TGF-β诱导的VEGF释放至关重要。

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