title: Cooperation of myocardin and Smad2 in inducing differentiation of mesenchymal stem cells into smooth muscle cells.
abstract: 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-β (TGF-β). However, the relationship or link between myocardin and TGF-β3-induced MSC differentiation has not been fully elucidated. Here, we demonstrated that both myocardin and TGF-β3 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 SM22α promoter and significantly enhance the expression of SM22α. Report assays with site-direct mutation analysis of SM22α promoter demonstrated that myocardin and Smad2 coactivated SM22α 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.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Guang-Da
authors.initials: GD
authors.lastname: Ren
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.forename: Ru-Fa
authors.initials: RF
authors.lastname: Yu
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004357:Drug Synergism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects; D000099251:Myocardin
chemical_list: D017931:DNA Primers; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051899:Smad2 Protein; D015534:Trans-Activators; D053782:Transforming Growth Factor beta3; D000099251:Myocardin; C497784:Smad2 protein, rat; C051615:transgelin