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PMID: 14676305 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells.

The Journal of cell biology ·Vol. 163 ·No. 6 ·2003-12-22 ·Pages 1303-11

Watabe T, Nishihara A, Mishima K, Yamashita J, Shimizu K, Miyazawa K, Nishikawa S, Miyazono K

Abstract

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.

MeSH Terms
Activins/metabolism,pharmacology Animals Benzamides/pharmacology Blood Vessels/cytology,embryology,metabolism Capillary Permeability/drug effects,physiology Cell Differentiation/drug effects,physiology Cell Division/drug effects,physiology Cells, Cultured Claudin-5 Dioxoles/pharmacology Endothelium, Vascular/cytology,metabolism Fetus Membrane Proteins/drug effects,metabolism Mice Neovascularization, Physiologic/drug effects,physiology Pluripotent Stem Cells/cytology,drug effects,metabolism Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta Stem Cells/cytology,drug effects,metabolism Tight Junctions/metabolism Transforming Growth Factor beta/metabolism,pharmacology Up-Regulation/drug effects,physiology
Chemicals
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide Benzamides Claudin-5 Cldn5 protein, mouse Dioxoles Membrane Proteins Receptors, Transforming Growth Factor beta Transforming Growth Factor beta Activins Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type I
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Watabe Tetsuro
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
Nishihara Ayako
Mishima Koichi
Yamashita Jun
Shimizu Kiyoshi
Miyazawa Keiji
Nishikawa Shin-Ichi
Miyazono Kohei
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200305147
Published
2003-12-22
Epub
2003-00-15
Pages
1303-11
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173713
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200305147 PMC Full Text View journal details
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