Cooperation of myocardin and smad2 in inducing differentiation of mesenchymal stem cells into smooth muscle cells

Several reports demonstrated that mesenchymal stem cells (MSCs) might differentiate into smooth muscle cells (SMCs) in vitro and in vivo. It has been shown that myocardin protein is a strong inducer of smooth muscle genes and MSCs can differentiate into SMCs in response to transforming growth factor-beta (TGF-beta). However, the relationship or link between myocardin and TGF-beta 3-induced MSC differentiation has not been fully elucidated. Here, we demonstrated that both myocardin and TGF-beta 3 were able to induce differentiation of rat bone marrow-derived MSCs toward smooth-muscle-like cell types, as evidenced by increasing expression of SMC-specific genes. Of note, myocardin cooperated with Smad2 to synergistically activate SM22a promoter and significantly enhance the expression of SM22a. Report assays with site-direct mutation analysis of SM22a promoter demonstrated that myocardin and Smad2 coactivated SM22a promoter mainly depending on CArG box and less on smad binding elements (SBE) sites as well. These findings reveal the cooperation of myocardin and Smad2 in process of MSC differentiation into SMCs. (C) 2012 IUBMB Life, 64(4): 331339, 2012