TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart
TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart
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DOI：
10.1006/dbio.1999.9211
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发表时间：
1999-04-15
影响因子：
2.7
通讯作者：
Runyan, RB
中科院分区：
文献类型：
--
作者：
Boyer, AS;Ayerinskas, II;Runyan, RB
心脏瓣膜的形成是由房室（AV）管内皮细胞的上皮-间充质细胞转化（EMT）发起的。由心脏emt形成的间充质细胞是心脏垫的初始细胞成分，也是瓣膜和间隔成纤维细胞的祖细胞。研究表明，转化生长因子β (TGF β)介导房室管内的EMT， TGF β 1和TGF β 2亚型在小鼠心脏中表达，TGF β 2和TGF β 3在鸟类心脏中表达。禽体内TGF β 3或小鼠体内TGF β 2的缺失导致心脏组织发育缺陷。这些观察结果提出了多个TGF β亚型是否参与瓣膜形成的问题。在本研究中，我们检测了TGF β 2和TGF β 3在鸡EMT过程中的定位和功能。TGF - β 2在EMT前后均存在于内皮细胞和心肌中。TGF β 2抗体抑制内皮细胞-细胞分离。相比之下，TGF β 3仅在EMT前存在于心肌中，在EMT开始时存在于内皮中。TGF β 3抗体抑制间充质细胞的形成和向基质的迁移。TGF β 2和TGF β 3均增加原纤维蛋白2的表达。然而，只有TGF β 2处理增加了细胞表面β -1,4-半乳糖转移酶的表达。这些数据表明，TGF β 2和TGF β 3依次、分别参与EMT的过程。TGF - β 2介导内皮细胞-细胞的初始分离，TGF - β 3则需要细胞形态学改变，使细胞迁移到下层ECM。(C) 1999学术出版社。
Heart valve formation is initiated by an epithelial-mesenchymal cell transformation (EMT) of endothelial cells in the atrioventricular (AV) canal. Mesenchymal cells formed from cardiac EMTs are the initial cellular components of the cardiac cushions and progenitors of valvular and septal fibroblasts. It has been shown that transforming growth factor beta (TGF beta) mediates EMT in the AV canal, and TGF beta 1 and 2 isoforms are expressed in the mouse heart while TGF beta 2 and 3 are expressed in the avian heart. Depletion of TGF beta 3 in avian or TGF beta 2 in mouse leads to developmental defects of heart tissue. These observations raise questions as to whether multiple TGF beta isoforms participate in valve formation. In this study, we examined the localization and function of TGF beta 2 and TGF beta 3 in the chick heart during EMT. TGF beta 2 was present in both endothelium and myocardium before and after EMT. TGF beta 2 antibody inhibited endothelial cell-cell separation. In contrast, TGF beta 3 was present only in the myocardium before EMT and was in the endothelium at the initiation of EMT. TGF beta 3 antibodies inhibited mesenchymal cell formation and migration into the underlying matrix. Both TGF beta 2 and 3 increased fibrillin 2 expression. However, only TGF beta 2 treatment increased cell surface beta-1,4-galactosyltransferase expression. These data suggest that TGF beta 2 and TGF beta 3 are sequentially and separately involved in the process of EMT. TGF beta 2 mediates initial endothelial cell-cell separation while TGF beta 3 is required for the cell morphological change that enables the migration of cells into the underlying ECM. (C) 1999 Academic Press.