期刊
EXPERIMENTAL CELL RESEARCH
卷 312, 期 18, 页码 3604-3619出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2006.08.006
关键词
endothelial cell; TGF beta; RhoGTPases; cytoskeleton; signal transduction; morphogenesis; angiogenesis
TGF beta is a potent regulator of cell differentiation in many cell types. On aortic endothelial cells, TGF beta 1 displays angiogenic properties in inducing capillary-like tube formation in collagen I gels, in vitro. We investigated cytoskeletal changes that precede tube formation and related these alterations to the effects of TGF beta 1 on the activation state of members of the RhoGTPase family. TGF beta 1 promotes cell elongation and stress fiber formation in aortic endothelial cells. Using cell lines with inducible expression of Rac1 mutants, we show that these events are mimicked by expression of dominant-negative Rac1 whereas the constitutively active mutant prevents the TGF beta 1-mediated change of phenotype. Although TGF beta 1 induces an initial rise in the Rac1-GTP content, this phase is followed by a prolonged loss of the active form. In contrast, RhoA activity increases progressively and reaches a plateau when Rac1-GTP is no longer detectable. Prolonged inhibition of Rac1 appears necessary and sufficient for the increase in RhoA-GTP. In situ examination of Rho activity in TGF beta 1-treated cells provides evidence that active RhoA relocalizes to the tips of elongated cells. inhibiting the Rho effector ROCK abrogates tube formation. Thus, Rac1 and RhoA are regulated by TGF beta 1 in the process of endothelial tube formation in Collagen I gels. (c) 2006 Elsevier Inc. All rights reserved.
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