TGFbeta1 regulates endothelial cell spreading and hypertrophy through a Rac-p38-mediated pathway.
Biol Cell
; 100(9): 537-50, 2008 Sep.
Article
in En
| MEDLINE
| ID: mdl-18387002
ABSTRACT
BACKGROUND INFORMATION TGFbeta (transforming growth factor beta) is a multifunctional cytokine and a potent regulator of cell growth, migration and differentiation in many cell types. In the vascular system, TGFbeta plays crucial roles in vascular remodelling, but the signalling pathways involved remain poorly characterized. RESULTS:
Using the model of porcine aortic endothelial cells, we demonstrated that TGFbeta stimulates cellular spreading when cells are on collagen I. TGFbeta-stimulated Rac1-GTP accumulation, which was associated with increased MAPK (mitogen-activated protein kinase) p38 phosphorylation. Furthermore, ectopic expression of a dominant-negative Rac mutant, or treatment of the cells with the p38 pharmacological inhibitor SB203580, abrogated TGFbeta-induced cell spreading. Our results demonstrate for the first time that prolonged exposure to TGFbeta stimulates endothelial cell hypertrophy and flattening. Collectively, these data indicate that TGFbeta-induced cell spreading and increase in cell surface areas occurs via a Rac-p38-dependent pathway.CONCLUSIONS:
The Rac-p38 pathway may have conceptual implications in pathophysiological endothelial cell responses to TGFbeta, such as wound healing or development of atherosclerotic lesions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MAP Kinase Signaling System
/
Endothelial Cells
/
Transforming Growth Factor beta1
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biol Cell
Year:
2008
Type:
Article