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, Raymond B Runyan

Research output: Contribution to journalArticle

211 Citations (Scopus)

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 (TGF/8) 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 TGF/33 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 epithelialmesenchymal 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
StatePublished - 1991
Externally publishedYes

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Epithelial-Mesenchymal Transition
Oligodeoxyribonucleotides
Transforming Growth Factors
Oligonucleotides
Endothelial Cells
Heart Valves
Stem Cells
Messenger RNA

Keywords

  • Cardiac development
  • Growth factors
  • Tissue interaction

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor β3",
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 (TGF/8) 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 TGF/33 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 epithelialmesenchymal cell transformation.",
keywords = "Cardiac development, Growth factors, Tissue interaction",
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T1 - Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor β3

AU - Potts, J. D.

AU - Dagle, J. M.

AU - Walder, J. A.

AU - Weeks, D. L.

AU - Runyan, Raymond B

PY - 1991

Y1 - 1991

N2 - 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 (TGF/8) 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 TGF/33 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 epithelialmesenchymal cell transformation.

AB - 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 (TGF/8) 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 TGF/33 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 epithelialmesenchymal cell transformation.

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KW - Tissue interaction

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