首页> 外文期刊>Artificial cells, nanomedicine, and biotechnology. >The hierarchical micro-anotextured topographies promote the proliferation and angiogenesis-related genes expression in human umbilical vein endothelial cells by initiation of Hedgehog-Gli1 signaling
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The hierarchical micro-anotextured topographies promote the proliferation and angiogenesis-related genes expression in human umbilical vein endothelial cells by initiation of Hedgehog-Gli1 signaling

机译:通过刺猬-Gli1信号的启动,分层的微观/纳米纹理形貌可促进人脐静脉内皮细胞的增殖和血管生成相关基因的表达

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The hierarchical microtexturedanotextured topographies have been recognized to have better tissue integration properties, but the underlying mechanisms are only partially understood. Hedgehog signaling plays a pivotal role in developmental and homeostatic angiogenesis. We suppose that the Hedgehog-Gli1 signaling may play a significant role in the response of endothelial cells to microtexturedanotextured topographies (MNTs). To confirm this hypothesis, we produced the MNTs decorated with TiO2 nanotubes of two different diameters (25 and 70?nm), and the proliferation, apoptosis, angiogenesis-related genes expression and Hedgehog signaling activity of human umbilical vein endothelial cells (HUVECs) grown onto these MNTs were measured. Our results showed that the MNTs induced significantly high expression of Sonic Hedgehog (SHH), Smoothened (SMO) and GLI1 in the HUVECs as well as high activation of Hedgehog-Gli1 signaling, compared to the smooth surface. The HUVECs grown on the MNTs showed significantly high levels of adhesion, proliferation and expression of angiogenesis-related genes, including angiopoietin-1 (ANG-1), vascular endothelial growth factor (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2) and endothelial nitric oxide synthase (ENOS); these enhancements were attenuated by siRNA-mediated depletion of SMO, which indicated a significant role of Hedgehog-Gli1 signaling in mediating the enhanced effect of the MNTs on the angiogenic potential of HUVECs. This study may contribute to the modification of biomaterial surfaces for better tissue integration and clinical performance.
机译:人们已经认识到,分层的微织构/纳米织构的地形图具有更好的组织整合特性,但是仅部分理解了潜在的机制。刺猬信号在发育和稳态血管生成中起关键作用。我们假设Hedgehog-Gli1信号传导可能在内皮细胞对微织构/纳米织构形貌(MNTs)的反应中起重要作用。为了证实这一假设,我们制备了用两种不同直径(25和70?nm)的TiO2纳米管修饰的MNT,以及生长的人脐静脉内皮细胞(HUVEC)的增殖,凋亡,血管生成相关基因表达和Hedgehog信号活性。在这些MNT上进行测量。我们的结果表明,与光滑表面相比,MNTs在HUVEC中诱导了Sonic Hedgehog(SHH),Smoothened(SMO)和GLI1的高表达以及Hedgehog-Gli1信号的高活化。在MNT上生长的HUVEC表现出显着高水平的粘附,增殖和表达血管生成相关基因,包括血管生成素1(ANG-1),血管内皮生长因子(VEGFA),血管内皮生长因子受体2(VEGFR2)和内皮型一氧化氮合酶(ENOS); siRNA介导的SMO耗竭减弱了这些增强作用,这表明Hedgehog-Gli1信号传导在介导MNT对HUVEC血管生成潜力的增强作用中起着重要作用。这项研究可能有助于生物材料表面的修饰,以获得更好的组织整合和临床性能。

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