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首页> 外文期刊>RSC Advances >Shear stress magnitude and transforming growth factor-beta eta 1 regulate endothelial to mesenchymal transformation in a three-dimensional culture microfluidic device
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Shear stress magnitude and transforming growth factor-beta eta 1 regulate endothelial to mesenchymal transformation in a three-dimensional culture microfluidic device

机译：剪切应力幅度和转化生长因子-βETA1调节三维培养微流体装置中的内部表心性转化

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摘要

Normal fibroblasts are present within the extracellular matrix (ECM). They can become activated, leading to increased proliferation and ECM protein secretion such as collagen type I to promote tissue remodeling. These cells are also involved in adult pathologies including cancer metastasis and cardiac and renal fibrosis. One source of activated fibroblasts is endothelial to mesenchymal transformation (EndMT), in which endothelial cells lose their cell-cell and cell-ECM adhesions, gain invasive properties, and become mesenchymal cells. While EndMT is well characterized in developmental biology, the mechanisms and functional role of EndMT in adult physiology and pathology have not been fully investigated. A microfluidic device with an incorporated three-dimensional ECM chamber was developed to study the role of combined steady fluid shear stress magnitudes and transforming growth factor-beta 1 (TGF-beta 1) on EndMT. Low (1 dyne per cm(2)) steady shear stress and TGF-beta 1 exposure induced EndMT in endothelial cells, including upregulation of mesenchymal protein and gene expression markers. Cells exposed to TGF-beta 1 and high (20 dynes per cm(2)) steady shear stress did not undergo EndMT, and protein and gene expression of mesenchymal markers was significantly downregulated. Mesenchymally transformed cells under static conditions with and without TGF-beta 1 showed significantly more collagen production when compared to fluidic conditions. These results confirm that both low shear stress and TGF-beta 1 induce EndMT in endothelial cells, but this process can be prevented by exposure to physiologically relevant high shear stress. These results also show conditions most likely to cause tissue pathology.
机译：正常成纤维细胞存在于细胞外基质（ECM）内。它们可以被激活，导致增加增殖和ECM蛋白质分泌，例如胶原蛋白I型以促进组织重塑。这些细胞也涉及成虫病理学，包括癌症转移和心脏和肾纤维化。活化成纤维细胞的一个来源是间充质转化（ENDMT）的内皮，其中内皮细胞失去了其细胞 - 细胞和细胞-ECM粘连，增益侵入性质，并成为间充质细胞。虽然Endmt在发育生物学中具有很好的特征，但尚未完全研究Endmt在成人生理学和病理学中的机制和功能作用。开发了一种具有掺入的三维ECM室的微流体装置，以研究组合稳定流体剪切应力幅度和转化生长因子-β1（TGF-BETA 1）对终生物的作用。低（1达因每厘米（2））稳定剪切应力和TGF-β1曝光诱导内皮细胞中的终止剂，包括开蛋白和基因表达标志物的上调。暴露于TGF-β1和高（每厘米/厘米（2））的细胞稳定剪切应力没有经历EndMT，并且间充质标记物的蛋白质和基因表达显着下调。与流体条件相比，具有和不具有TGF-β1的静态条件下的间质上转化的细胞显着增加胶原蛋白产生。这些结果证实，低剪切应力和TGF-β1诱导内皮细胞中的Endmt，但是通过暴露于生理相关的高剪切应力，可以防止该过程。这些结果还显示出最有可能引起组织病理学的条件。

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  • 来源
    《RSC Advances》 |2016年第88期|共11页
  • 作者

    Mina Sara G.; Wang Wei; Cao Qingfeng; Huang Peter; Murray Bruce T.; Mahler Gretchen J.;

  • 作者单位

    SUNY Binghamton Dept Biomed Engn POB 6000 Binghamton NY 13902 USA;

    SUNY Binghamton Dept Mech Engn Binghamton NY 13902 USA;

    SUNY Binghamton Dept Mech Engn Binghamton NY 13902 USA;

    SUNY Binghamton Dept Mech Engn Binghamton NY 13902 USA;

    SUNY Binghamton Dept Mech Engn Binghamton NY 13902 USA;

    SUNY Binghamton Dept Biomed Engn POB 6000 Binghamton NY 13902 USA;

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  • 中图分类 化学;
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