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- Title
A novel mechanism of TGFβ-induced actin reorganization mediated by Smad proteins and Rho GTPases.
- Authors
Vardouli, Lina; Vasilaki, Eleftheria; Papadimitiou, Elsa; Kardassis, Dimitris; Stournaras, Christos
- Abstract
In previous studies, we have demonstrated that RhoA/B-dependent signaling regulates TGFβ-induced rapid actin reorganization in Swiss 3T3 fibroblasts. Here we report that TGFβ regulates long-term actin remodeling by increasing the steady-state mRNA levels of the RhoB gene in mouse Swiss 3T3 fibroblasts and human hepatoma HepG2 cells. We show that this regulation is specific for the RhoB gene and is facilitated by enhanced activity of the RhoB promoter. Adenovirus-mediated gene transfer of Smad2 and Smad3 in Swiss 3T3 fibroblasts induced transcription of the endogenous RhoB gene but not the RhoA gene. Interestingly, in JEG-3 choriocarcinoma cells that lack endogenous Smad3, TGFβ-induced transcriptional up-regulation of the RhoB gene was not observed, but it was restored by adenoviral Smad3 overexpression. In addition, Smad2 and Smad3 triggered activation of RhoA and RhoB GTPases and long-term actin reorganization in Swiss 3T3 fibroblasts. Finally, Smad3, and to a lesser extent Smad2, induced transcription of the α-smooth muscle actin ( α-SMA) gene, and enhanced the incorporation of α-SMA into microfilaments in Swiss 3T3 fibroblasts. These data reveal a novel mechanism of cross-talk between the classical TGFβ/Smad pathway and Rho GTPases, regulating the rapid and the long-term actin reorganization that may control the fibroblast–myofibroblast differentiation program.
- Subjects
BIOCHEMICAL mechanism of action; TRANSFORMING growth factors-beta; ACTIN; RHO GTPases; CYTOPLASMIC filaments; ADENOVIRUSES; FIBROBLASTS
- Publication
FEBS Journal, 2008, Vol 275, Issue 16, p4074
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2008.06549.x