首页> 美国卫生研究院文献>The Journal of Clinical Investigation >Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.
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Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.

机译:体外血管生成过程中微血管内皮细胞上转化生长因子β受体水平的调节。

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摘要

Microvascular endothelial cells (RFCs) cultured in two-dimensional (2D) cultures proliferate rapidly and exhibit an undifferentiated phenotype. Addition of transforming growth factor beta1 (TGFbeta1) increases fibronectin expression and inhibits proliferation. RFCs cultured in three-dimensional (3D) type I collagen gels proliferate slowly and are refractory to the anti-proliferative effects of TGF beta1. TGF beta1 promotes tube formation in 3D cultures. TGF beta1 increases fibronectin expression and urokinase plasminogen activator (uPA) activity and plasminogen activator inhibitor-1 (PAI-1) levels in 3D cultures. Since the TGF beta type I and II receptors have been reported to regulate different activities induced by TGF beta1, we compared the TGF beta receptor profiles on cells in 2D and 3D cultures. RFCs in 3D cultures exhibited a significant loss of cell surface type II receptor compared with cells in 2D cultures. The inhibitory effect of TGF beta1 on proliferation is suppressed in transfected 2D cultures expressing a truncated form of the type II receptor, while its stimulatory effect on fibronectin production is reduced in both 2D and 3D transfected cultures expressing a truncated form of the type I receptor. These data suggest that the type II receptor mediates the antiproliferative effect of TGF beta1 while the type I receptor mediates the matrix response of RFCs to TGF beta1 and demonstrate that changes in the matrix environment can modulate the surface expression of TGF beta receptors, altering the responsiveness of RFCs to TGF beta1.
机译:在二维(2D)培养物中培养的微血管内皮细胞(RFC)迅速增殖,并表现出未分化的表型。添加转化生长因子beta1(TGFbeta1)会增加纤连蛋白的表达并抑制增殖。在三维(3D)I型胶原蛋白凝胶中培养的RFC增殖缓慢,并且对TGF beta1的抗增殖作用具有抵抗力。 TGF beta1促进3D文化中的管形成。 TGF beta1可提高3D培养物中纤连蛋白的表达,尿激酶纤溶酶原激活物(uPA)活性和纤溶酶原激活物抑制剂1(PAI-1)的水平。由于已经报道了I型和II型TGFβ受体可调节TGFβ1诱导的不同活性,因此我们比较了2D和3D培养细胞中TGFβ受体的概况。与2D培养中的细胞相比,3D培养中的RFC表现出细胞表面II型受体的显着丧失。在表达II型受体的截短形式的转染2D培养物中,TGF beta1对增殖的抑制作用被抑制,而在表达I型受体的截短形式的2D和3D转染的培养物中,其对纤连蛋白产生的刺激作用均降低。这些数据表明,II型受体介导TGF beta1的抗增殖作用,而I型受体介导RFC对TGF beta1的基质反应,并表明基质环境的变化可以调节TGFβ受体的表面表达,从而改变响应性。 RFC转换为TGF beta1。

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