TAILIEUCHUNG - Báo cáo khoa học: A novel mechanism of TGFb-induced actin reorganization mediated by Smad proteins and Rho GTPases

In previous studies, we have demonstrated that RhoA⁄B-dependent signal-ing regulates TGFb-induced rapid actin reorganization in Swiss 3T3 fibro-blasts. Here we report that TGFbregulates long-term actin remodeling by increasing the steady-state mRNA levels of the RhoBgene in mouse Swiss 3T3 fibroblasts and human hepatoma HepG2 cells. | ễFEBS Journal A novel mechanism of TGFp-induced actin reorganization mediated by Smad proteins and Rho GTPases Lina Vardouli1 Eleftheria Vasilaki1 2 Elsa Papadimitriou1 Dimitris Kardassis1 2 and Christos Stournaras1 1 Department of Biochemistry Schoolof Medicine University of Crete Heraklion Greece 2 Institute of Molecular Biology and Biotechnology Foundation for Research Technology-Hellas Heraklion Greece Keywords actin Rho GTPases Smad TGFP a-SMA Correspondence C. Stournaras Department of Biochemistry Schoolof Medicine University of Crete GR-71110 Heraklion Greece Fax 30 2810 394530 Tel 30 2810 394563 E-mail cstourn@ Received 22 April2008 revised 1 June 2008 accepted 12 June 2008 doi In previous studies we have demonstrated that RhoA B-dependent signaling regulates TGFp-induced rapid actin reorganization in Swiss 3T3 fibroblasts. Here we report that TGFb 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 TGFb-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 a-smooth muscle actin a-SMA gene and enhanced the incorporation of a-SMA into microfilaments in Swiss 3T3 fibroblasts. These data reveal a novel mechanism of cross-talk between the classical TGFp Smad pathway and Rho GTPases regulating the .

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