Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor β3

J. D. Potts, J. M. Dagle, J. A. Walder, D. L. Weeks, R. B. Runyan

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Abstract

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 TGFβ1, -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, TGFβ3, is essential for the epithelial-mesenchymal cell transformation.

Original languageEnglish (US)
Pages (from-to)1516-1520
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number4
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

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Keywords

  • cardiac development
  • growth factors
  • tissue interaction

ASJC Scopus subject areas

  • General

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