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PMID: 1996351 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 4 ·1991-02-15 ·Pages 1516-20

Potts JD, Dagle JM, Walder JA, Weeks DL, Runyan RB

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 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.

MeSH Terms
Animals Base Sequence Cell Differentiation/drug effects Chick Embryo Endothelium/cytology Epithelial Cells Heart/embryology Molecular Sequence Data Myocardium/cytology Oligonucleotides, Antisense/pharmacology RNA Probes RNA, Messenger/analysis,genetics Transforming Growth Factor beta/genetics,physiology
Chemicals
Oligonucleotides, Antisense RNA Probes RNA, Messenger Transforming Growth Factor beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Potts J D
Department of Anatomy, University of Iowa, Iowa City 52242.
Dagle J M
Walder J A
Weeks D L
Runyan R B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.4.1516
Published
1991-02-15
Pages
1516-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51050
Subset
IM
Grants
NIGMS NIH HHS · GM07228 · United States
NHLBI NIH HHS · HL42266 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.4.1516 PMC Full Text View journal details
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