Retinoic acid inhibition of cardiac mesenchyme formation in vitro correlates with changes in the secretion of particulate matrix from the myocardium.
Retinoic acid has been associated with a variety of cardiac defects. A percentage of these defects are related to changes in the endocardial cushions. Studies in mice and older chick embryos have shown a decrease in mesenchymal cell formation attributable to retinoic acid and have suggested that retinoic acid was affecting the extracellular matrix. In this study we have tested the effect of retinoic acid on cardiac mesenchyme formation in vitro and then tested retinoic acid treated myocyte cultures for changes in the expression of hLAMP-1, fibronectin and transferrin members of the particulate matrix that is required for mesenchyme formation. Initial experiments tested the effect of retinoic acid on mesenchymal cell formation first in atrioventricular canal and outflow tract explant cultures and then in AV endothelial monolayer cultures using myocyte conditioned media or the particulate matrix fraction from retinoic acid treated myocyte cultures. In all cases, mesenchymal cell formation was suppressed while no suppression was observed when MyoCM was included with retinoic acid. Protein analysis showed that retinoic acid had a stimulatory effect on protein synthesis. ELISA assays revealed that retinoic acid treated myocyte cultures contained significantly more hLAMP-1 and fibronectin than either normal or DMSO controls. However, transferrin was not affected by retinoic acid treatment in these experiments. Our results suggest that retinoic acid affects the expression of the particulate matrix and that these changes may be responsible for the observed decrease in mesenchymal cell formation.
Yan
M
M
Department of Anatomy, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Nick
T G
TG
Sinning
A R
AR
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D002642:Chick Embryo; D017077:Culture Media, Conditioned; D004699:Endocardium / Q000187:drug effects / Q000196:embryology; D005353:Fibronectins / Q000032:analysis; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000032:analysis; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009206:Myocardium / Q000166:cytology; D009924:Organ Culture Techniques; D014168:Transferrin / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D005353:Fibronectins; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D014168:Transferrin; D014212:Tretinoin