EPITHELIAL MESENCHYMAL TRANSFORMATION OF EMBRYONIC CARDIAC ENDOTHELIAL-CELLS IS INHIBITED BY A MODIFIED ANTISENSE OLIGODEOXYNUCLEOTIDE TO TRANSFORMING GROWTH-FACTOR BETA-3
EPITHELIAL MESENCHYMAL TRANSFORMATION OF EMBRYONIC CARDIAC ENDOTHELIAL-CELLS IS INHIBITED BY A MODIFIED ANTISENSE OLIGODEOXYNUCLEOTIDE TO TRANSFORMING GROWTH-FACTOR BETA-3
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DOI：
10.1073/pnas.88.4.1516
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发表时间：
1991-02-01
影响因子：
11.1
通讯作者：
RUNYAN, RB
中科院分区：
文献类型：
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作者：
POTTS, JD;DAGLE, JM;RUNYAN, RB
在心脏发育早期，心脏瓣膜和膜隔的祖细胞经历上皮-间充质转化。 以前的研究表明，这种转化取决于心脏产生的转化生长因子-β（TGF-β）分子的活性。 在本研究中，我们使用了修饰的反义寡脱氧核苷酸产生的非保守区域的TGF-β-1，2，-3，和-4，以检查这些成员在这一转变的可能作用。 与TGF-β-3 mRNA互补的氨基磷酸酯修饰的寡核苷酸能够抑制80%的正常上皮-间充质转化。 针对TGF-β-3的未修饰的寡核苷酸、针对TGF-β-1、-2和-4的修饰的寡核苷酸以及两种修饰的对照寡核苷酸不能抑制转化。 这些数据表明，TGF-β家族的特定成员TGF-β-3对于上皮-间充质细胞转化是必需的。
During early cardiac development, the progenitor cells of the heart valves and membranous septa undergo an epithelial-mesenchymal transformation. Previous studies have shown that this transformation depends on the activity of a transforming growth factor-beta (TGF-beta) molecule produced by the heart. In the present study, we have used modified antisense oligodeoxynucleotides generated to nonconserved regions of TGF-beta-1, -2, -3, and -4 to examine the possible roles of these members in this transformation. A phosphoramidate-modified oligonucleotide complementary to TGF-beta-3 mRNA was capable of inhibiting normal epithelial-mesenchymal transformation by 80%. Unmodified oligonucleotides to TGF-beta-3, modified oligonucleotides to TGF-beta-1, -2, and -4, and two modified control oligonucleotides were unable to inhibit the transformation. These data demonstrate that a specific member of the TGF-beta family, TGF-beta-3, is essential for the epithelial-mesenchymal cell transformation.