Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3.
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.
Potts
J D
JD
Department of Anatomy, University of Iowa, Iowa City 52242.
Dagle
J M
JM
Walder
J A
JA
Weeks
D L
DL
Runyan
R B
RB
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D002642:Chick Embryo; D004727:Endothelium / Q000166:cytology*; D004847:Epithelial Cells; D006321:Heart / Q000196:embryology*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D016376:Oligonucleotides, Antisense; D015347:RNA Probes; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta