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Nanopatterned polymer substrates promote endothelial proliferation by initiation of β-catenin transcriptional signaling

机译:纳米图案的聚合物底物通过启动β-catenin转录信号传导来促进内皮细胞增殖

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Control of endothelial phenotype involves a variety of signaling pathways and transcriptional regulators, including the junctional protein β-catenin. This multifunctional signaling molecule is part of adhesion contacts in the endothelium and is able to translocate into the nucleus to activate genetic programs and control proliferation and the fate of the cells. We investigated the influence of laser-generated nanopatterns on polymeric cell culture substrates on endothelial tissue architecture, proliferation and β-catenin signaling. For our experiments human microvascular endothelial cells or CD34 + endothelial progenitor cells, isolated from human adipose tissue, were cultured on polyethylene terephthalate (PET) substrates with oriented nanostructures with lateral periodicities of 1.5 μm and 300 nm, respectively. The surface topography and chemistry of the PET substrates were characterized by electron microscopy, atomic force microscopy, water contact angle measurement and X-ray photoelectron spectroscopy. Analysis of cell phenotype markers as well as β-catenin signaling revealed that short-term culture of endothelial cells on nanostructured substrates generates a proliferative cell phenotype associated with nuclear accumulation of β-catenin and activation of specific β-catenin target genes. The effects of the nanostructures were not directly correlated with nanostructure-induced alignment of cells and were also clearly distinguishable from the effects of altered PET surface chemistry due to photomodification. In summary, we present a novel mechanism of surface topology-dependent control of transcriptional programs in mature endothelium and endothelial progenitor cells.
机译:内皮表型的控制涉及多种信号通路和转录调节子,包括连接蛋白β-catenin。该多功能信号分子是内皮中粘附接触的一部分,能够转移到细胞核中以激活遗传程序并控制细胞的增殖和命运。我们调查了激光生成的纳米模式对内皮细胞结构,增殖和β-catenin信号的聚合物细胞培养基质的影响。对于我们的实验,将从人脂肪组织中分离出来的人微血管内皮细胞或CD34 +内皮祖细胞培养在具有定向纳米结构且横向周期性分别为1.5μm和300 nm的聚对苯二甲酸乙二醇酯(PET)基质上。通过电子显微镜,原子力显微镜,水接触角测量和X射线光电子能谱对PET基材的表面形貌和化学特性进行了表征。细胞表型标志物以及β-catenin信号的分析显示,内皮细胞在纳米结构底物上的短期培养会产生增殖性细胞表型,与β-catenin的核积累和特定β-catenin靶基因的激活有关。纳米结构的影响与纳米结构诱导的细胞排列没有直接关系,并且也可以与由于光改性而改变的PET表面化学的影响区分开。总而言之,我们提出了一种成熟的内皮细胞和内皮祖细胞中转录程序的表面拓扑依赖控制的新机制。

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