Epithelial-Mesenchymal Transformation of Embryonic Cardiac Endothelial Cells is Inhibited by a Modified Antisense Oligodeoxynucleotide to Transforming Growth Factor β3

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 β (TGFβ) molecule produced by the heart. In the present study, we have used modified antisense oligodeoxynucleotides generated to nonconserved regions of TGFβ 1, -2, -3, and -4 to examine the possible roles of these members in this transformation. A phosphoramidate-modified oligonucleotide complementary to TGFβ3 mRNA was capable of inhibiting normal epithelial-mesenchymal transformation by 80%. Unmodified oligonucleotides to TGFβ3, modified oligonucleotides to TGFβ1, -2, and -4, and two modified control oligonucleotides were unable to inhibit the transformation. These data demonstrate that a specific member of the TGFβ family, TGFβ 3, is essential for the epithelial-mesenchymal cell transformation.