TGFβ type III and TGFβ type II receptors have distinct activities during epithelial-mesenchymal cell transformation in the embryonic heart
TGFβ type III and TGFβ type II receptors have distinct activities during epithelial-mesenchymal cell transformation in the embryonic heart
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DOI：
10.1002/dvdy.1154
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发表时间：
2001-08-01
影响因子：
2.5
通讯作者：
Runyan, RB
中科院分区：
文献类型：
--
作者：
Boyer, AS;Runyan, RB
在心脏发育的早期阶段，心脏瓣膜和间隔的祖细胞通过一个被称为“上皮-间充质细胞转化”的发育过程来自内皮细胞。这一过程仅限于胚胎心脏的房室管和流出道部分。TGF β信号转导通路在心脏发育过程中上皮-间充质细胞转化过程中起关键作用。先前，我们发现TGF β II型（T β RII）和III型（T β RIII）受体都需要介导鸡心脏上皮间充质细胞的转化。此外，不同的TGF β 2和TGF β 3活性对应于胚胎细胞转化过程的不同组成部分。其他人对TGF β介导的细胞增殖抑制的研究得出了T β RIII通过促进TGF β 2与T β RII结合而起作用的模型。在本研究中，我们提供的证据表明，T β RIII介导不同于T β RII的细胞反应。针对T β RIII的阻断抗体，而不是针对T β RII的抗体，特异性地抑制内皮细胞-细胞分离步骤。通过阻断T β RIII抗体对发育标志物进行检查，发现其表达模式与T β RII抗体治疗明显不同。这些数据表明，在上皮间充质细胞转化过程中，内皮细胞-细胞分离需要一个独特的T β iii介导的过程。由于TGF β 2介导内皮细胞-细胞分离，数据表明TGF β 2与T β RIII在上皮间充质细胞转化的细胞分离步骤中存在特异性关联。我们得出结论，不同的T β RII和T β RIII信号转导途径介导心脏上皮-间质细胞转化。(C) 2001 Wiley-Liss, Inc。
During the early stages of heart development, progenitors for the heart valves and septa come from endothelial cells via a developmental process known as "epithelial-mesenchymal cell transformation." This process is restricted to the atrioventricular (AV) canal and outflow tract portions of the embryonic heart. TGF beta signal transduction pathways play critical roles during epithelial-mesenchymal cell transformation in heart development. Previously, we showed that both TGF beta Type II (T beta RII) and Type III (T beta RIII) receptors are required to mediate epithelial mesenchymal cell transformation in chick heart. Further, distinct TGF beta2 and TGF beta3 activities correspond to separate components of the embryonic cell transformation process. Studies by others of TGF beta -mediated inhibition of cell proliferation produced a model where T beta RIII functions by facilitating TGF beta2 binding to T beta RII. In the present study, we provide evidence that T beta RIII mediates distinct cellular responses from those of T beta RII. Blocking antibody for T beta RIII, but not antibody against T beta RII, specifically inhibits the endothelial cell-cell separation step. Examination of developmental markers, perturbed by blocking T beta RIII antibody, revealed a pattern of expression distinctively different from that of T beta RII antibody treatment. These data show that a distinct T beta RIII-mediated process is required for endothelial cell-cell separation during epithelial mesenchymal cell transformation. As TGF beta2 mediates endothelial cell-cell separation, the data point to a specific association of TGF beta2 and T beta RIII in the cell separation step of epithelial mesenchymal cell transformation. We conclude that distinct T beta RII and T beta RIII signal transduction pathways mediate epithelial-mesenchymal cell transformation in the heart. (C) 2001 Wiley-Liss, Inc.