TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells.
Recent findings have shown that embryonic vascular progenitor cells are capable of differentiating into mural and endothelial cells. However, the molecular mechanisms that regulate their differentiation, proliferation, and endothelial sheet formation remain to be elucidated. Here, we show that members of the transforming growth factor (TGF)-beta superfamily play important roles during differentiation of vascular progenitor cells derived from mouse embryonic stem cells (ESCs) and from 8.5-days postcoitum embryos. TGF-beta and activin inhibited proliferation and sheet formation of endothelial cells. Interestingly, SB-431542, a synthetic molecule that inhibits the kinases of receptors for TGF-beta and activin, facilitated proliferation and sheet formation of ESC-derived endothelial cells. Moreover, SB-431542 up-regulated the expression of claudin-5, an endothelial specific component of tight junctions. These results suggest that endogenous TGF-beta/activin signals play important roles in regulating vascular growth and permeability.
Watabe
Tetsuro
T
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
Nishihara
Ayako
A
Mishima
Koichi
K
Yamashita
Jun
J
Shimizu
Kiyoshi
K
Miyazawa
Keiji
K
Nishikawa
Shin-Ichi
S
Miyazono
Kohei
K
D028341:Activins / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D062507:Claudin-5; D004149:Dioxoles / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005333:Fetus; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D062507:Claudin-5; C491511:Cldn5 protein, mouse; D004149:Dioxoles; D008565:Membrane Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D028341:Activins; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I