Open AccessSmad7 Promotes and Enhances Skeletal Muscle Differentiation
Author(s) -
Helen D. Kollias,
Robert L. Perry,
Tetsuaki Miyake,
Arif Aziz,
John C. McDermott
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00384-06
Subject(s) - myogenesis , myod , myostatin , myod protein , biology , skeletal muscle , myogenin , pitx2 , myocyte , c2c12 , cellular differentiation , microbiology and biotechnology , transcription factor , endocrinology , genetics , homeobox , gene
Transforming growth factor β1 (TGF-β1) and myostatin signaling, mediated by the same Smad downstream effectors, potently repress skeletal muscle cell differentiation. Smad7 inhibits these cytokine signaling pathways. The role of Smad7 during skeletalmuscle cell differentiation was assessed. In these studies, we document that increased expression of Smad7 abrogates myostatin- but notTGF-β1-mediated repression of myogenesis. Further, constitutiveexpression of exogenous Smad7 potently enhanced skeletal muscledifferentiation and cellular hypertrophy. Conversely, targeting ofendogenous Smad7 by small interfering RNA inhibited C2C12 muscle celldifferentiation, indicating an essential role for Smad7 duringmyogenesis. Congruent with a role for Smad7 in myogenesis, we observedthat the muscle regulatory factor (MyoD) binds to and transactivatesthe Smad7 proximal promoter region. Finally, we document that Smad7directly interacts with MyoD and enhances MyoD transcriptionalactivity. Thus, Smad7 cooperates with MyoD, creating a positive loop toinduce Smad7 expression and to promote MyoD driven myogenesis. Takentogether, these data implicate Smad7 as a fundamental regulator ofdifferentiation in skeletal musclecells.