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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
TGF-beta signaling in embryonic stem cell-derived endothelial cells
Tetsuro Watabe1, Jun K Yamashita, Koichi Mishima
1Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Japan.
Transforming growth factor-beta (TGF-β) signaling is crucial for vascular progenitor cell differentiation. Inhibiting TGF-β signaling with SB-431542 promotes endothelial cell proliferation and sheet formation.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- The transforming growth factor (TGF)-beta superfamily plays a critical role in vascular development.
- Mutations in TGF-beta signaling components lead to vascular defects in humans and mice.
- Embryonic stem cell (ESC)-derived vascular progenitor cells can differentiate into endothelial and mural cells.
Purpose of the Study:
- To investigate the role of TGF-beta superfamily members in the differentiation of mouse ESC-derived vascular progenitor cells.
- To examine the effects of TGF-beta and its inhibitors on ESC-derived endothelial cell proliferation and function.
- To analyze the downstream signaling pathways activated by TGF-beta and BMP in these cells.
Main Methods:
- Utilized mouse ESCs to generate vascular progenitor cells.
- Applied TGF-beta and SB-431542 (a TGF-β/activin receptor kinase inhibitor) to study cellular effects.
- Assessed cell proliferation and sheet formation.
- Analyzed Smad2 and Smad1/5 phosphorylation via Western blotting.
Main Results:
- TGF-beta inhibited proliferation and sheet formation of ESC-derived endothelial cells.
- SB-431542 treatment enhanced proliferation and sheet formation.
- TGF-beta induced phosphorylation of Smad2 and Smad1/5.
- Bone morphogenetic protein (BMP) induced phosphorylation of Smad1/5.
Conclusions:
- TGF-beta superfamily signaling significantly influences the differentiation and behavior of ESC-derived endothelial cells.
- Inhibition of TGF-beta signaling can promote endothelial cell proliferation and sheet formation, suggesting therapeutic potential.
- Understanding these signaling pathways is crucial for regenerative medicine applications involving vascularization.
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