Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells.
Inhibition by all-trans retinoic acid (atRA) of the microvasculature formation in chicken chorioallantoic membrane (CAM) accompanied remarkably reduced numbers of endothelial cells (ECs) and increased numbers of mural cells (MCs) under the chorionic epithelial layer. Ro41-5253 (retinoid antagonist) exerted the opposite effect. Although atRA did not affect the differentiation of murine embryonic stem cell-derived vascular progenitor cells (VPCs) into ECs or MCs, atRA suppressed EC-MC interaction, leading to impaired branching. In both atRA-treated VPC cultures and CAM tissues underneath the chorionic epithelial layer, the expression of angiopoietin-2 (Ang-2; competitor for Ang-1) was enhanced, whereas that of Tie2 (a receptor for Angs) was reduced. Simultaneous treatment with Ang-1 partially blocked RA induction of EC-MC malinteraction and reduction in blood vessel formation. These results suggest that retinoid(s) may reduce EC-MC interaction by down-regulating Tie2 signaling as well as decreased EC numbers, which lead to impaired vascular remodeling.
Suzuki
Yasuhiro
Y
Molecular Cellular Pathology Research Unit, RIKEN-Institute for Physical and Chemical Research, Wako, Saitama, Japan.
Komi
Yusuke
Y
Ashino
Hiromi
H
Yamashita
Jun
J
Inoue
Jun
J
Yoshiki
Atsushi
A
Eichmann
Anne
A
Amanuma
Hiroshi
H
Kojima
Soichi
S
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D042682:Angiopoietins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D042682:Angiopoietins; D017931:DNA Primers; D008565:Membrane Proteins; D014212:Tretinoin; D042787:Receptor, TIE-2