EPITHELIAL MESENCHYMAL TRANSFORMATION OF EMBRYONIC CARDIAC ENDOTHELIAL-CELLS IS INHIBITED BY A MODIFIED ANTISENSE OLIGODEOXYNUCLEOTIDE TO TRANSFORMING GROWTH-FACTOR BETA-3

被引:244
作者
POTTS, JD
DAGLE, JM
WALDER, JA
WEEKS, DL
RUNYAN, RB
机构
[1] UNIV IOWA HOSP & CLIN,DEPT ANAT,IOWA CITY,IA 52242
[2] INTEGRATED DNA TECHNOL INC,CORALVILLE,IA 52241
[3] UNIV IOWA HOSP & CLIN,DEPT BIOCHEM,IOWA CITY,IA 52242
关键词
GROWTH FACTORS; CARDIAC DEVELOPMENT; TISSUE INTERACTION;
D O I
10.1073/pnas.88.4.1516
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:1516 / 1520
页数:5
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