Antisense oligodeoxynucleotide complementary to smooth muscle alpha-actin inhibits endothelial-mesenchymal transformation during chick cardiogenesis.
alpha-Smooth-muscle actin (SMA) is the major isoform of adult vascular tissues. During early development, SMA is expressed in various mesodermally derived tissues in a spatiotemporally restricted manner; however, its exact role remains unknown. We examined its role in the formation of chicken atrioventricular (AV) endocardial cushion tissue. This developmental process possesses the characteristics of endothelial-mesenchymal transformation and is partly TGF beta-dependent. Immunohistochemistry showed that SMA was (1) expressed homogeneously in the newly formed appendages of transforming endothelial/mesenchymal cells, and (2) distributed in a punctate manner in the lamellipodia/filopodia of invading mesenchymal cells. Antisense oligodeoxynucleotide (ODNs) specific for SMA reduced both SMA expression and mesenchymal formation in AV endothelial cells cultured with myocardium on a collagen gel lattice. Perturbation of SMA by antisense ODN also inhibited TGF beta-inducible migratory appendage formation in a cultured AV endothelial monolayer. However, it did not inhibit cell:cell separation or cellular hypertrophy. These results suggest that the expression of SMA is necessary for migratory appendage formation during the TGF beta-dependent initial phenotypic changes that occur in endothelial-mesenchymal transformation.
Nakajima
Y
Y
Department of Anatomy, Saitama Medical School, Japan. yuji@saitama-med.ac.jp
Yamagishi
T
T
Yoshimura
K
K
Nomura
M
M
Nakamura
H
H
D000199:Actins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000187:drug effects / Q000196:embryology*; D019084:Fluorescent Antibody Technique, Indirect; D006321:Heart / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis
D000199:Actins; D020319:Oligodeoxyribonucleotides, Antisense; D016212:Transforming Growth Factor beta