Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis
Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis
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DOI：
10.1172/jci118565
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发表时间：
1996-03-15
影响因子：
15.9
通讯作者：
Madri, JA
中科院分区：
文献类型：
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作者：
Sankar, S;MahootiBrooks, N;Madri, JA
在二维（2D）培养基中培养的微血管内皮细胞（rfc）增殖迅速，表现出未分化的表型。添加转化生长因子β 1 （TGF β 1）可增加纤维连接蛋白表达，抑制细胞增殖。在三维（3D） I型胶原凝胶中培养的rfc增殖缓慢，对TGF β 1的抗增殖作用难起作用。TGF β 1促进三维培养中的管形成。TGF β 1增加三维培养中纤维连接蛋白表达、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）水平。由于已有报道TGF β I型和II型受体调节TGF β 1诱导的不同活性，我们比较了2D和3D培养细胞上TGF β受体的特征。与2D培养的细胞相比，3D培养的rfc表现出明显的细胞表面II型受体缺失。TGF β 1对增殖的抑制作用在表达II型受体截断形式的转染2D培养物中被抑制，而在表达I型受体截断形式的转染2D和3D培养物中，其对纤维连接蛋白产生的刺激作用都被降低。这些数据表明，II型受体介导TGF β 1的抗增殖作用，而I型受体介导rfc对TGF β 1的基质应答，表明基质环境的改变可以调节TGF β受体的表面表达，改变rfc对TGF β 1的应答性。
Microvascular endothelial cells (RFCs) cultured in two-dimensional (2D) cultures proliferate rapidly and exhibit an undifferentiated phenotype. Addition of transforming growth factor beta 1 (TGF beta 1) 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 beta 1. TGF beta 1 promotes tube formation in 3D cultures. TGF beta 1 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 beta 1, 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 beta 1 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 beta 1 while the type I receptor mediates the matrix response of RFCs to TGF beta 1 and demonstrate that changes in the matrix environment can modulate the surface expression of TGF beta receptors, altering the responsiveness of RFCs to TGF beta 1.