TGFbeta1 regulates endothelial cell spreading and hypertrophy through a Rac-p38-mediated pathway.
BACKGROUND
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.
Varon
Christine
C
European Institute of Chemistry and Biology, Pessac, F-33600 France.
Rottiers
Patricia
P
Ezan
Jerome
J
Reuzeau
Edith
E
Basoni
Caroline
C
Kramer
Ijsbrand
I
Génot
Elisabeth
E
D000818:Animals; D002460:Cell Line; D048430:Cell Shape; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006984:Hypertrophy; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580