TGFβ1 regulates endothelial cell spreading and hypertrophy through a Rac-p38-mediated pathway

Christine Varon, Patricia Rottiers, Jerome Ezan, Edith Reuzeau, Caroline Basoni, IJsbrand Kramer, Elisabeth Génot
Biology of the Cell. 2008-09-01; 100(9): 537-550
DOI: 10.1042/BC20080021

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1. Biol Cell. 2008 Sep;100(9):537-50. doi: 10.1042/BC20080021.

TGFbeta1 regulates endothelial cell spreading and hypertrophy through a
Rac-p38-mediated pathway.

Varon C(1), Rottiers P, Ezan J, Reuzeau E, Basoni C, Kramer I, Génot E.

Author information:
(1)European Institute of Chemistry and Biology, Pessac, F-33600 France.

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.

DOI: 10.1042/BC20080021
PMID: 18387002 [Indexed for MEDLINE]


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