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TGFβ1 regulates endothelial cell spreading and hypertrophy through a Rac—p38‐mediated pathway
Author(s) -
Varon Christine,
Rottiers Patricia,
Ezan Jerome,
Reuzeau Edith,
Basoni Caroline,
Kramer IJsbrand,
Génot Elisabeth
Publication year - 2008
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20080021
Subject(s) - microbiology and biotechnology , biology , transforming growth factor , signal transduction , mapk/erk pathway , p38 mitogen activated protein kinases , cell growth , endothelial stem cell , ectopic expression , cell , rac1 , cell culture , biochemistry , genetics , in vitro
Background information . TGFβ (transforming growth factor β) is a multifunctional cytokine and a potent regulator of cell growth, migration and differentiation in many cell types. In the vascular system, TGFβ 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 TGFβ stimulates cellular spreading when cells are on collagen I. TGFβ‐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 TGFβ‐induced cell spreading. Our results demonstrate for the first time that prolonged exposure to TGFβ stimulates endothelial cell hypertrophy and flattening. Collectively, these data indicate that TGFβ‐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 TGFβ, such as wound healing or development of atherosclerotic lesions.