ABSTRACT
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 skeletal
muscle cell differentiation was assessed. In these studies, we document that increased expression of Smad7 abrogates myostatin- but not
TGF-β1-mediated repression of myogenesis. Further, constitutive
expression of exogenous Smad7 potently enhanced skeletal muscle
differentiation and cellular hypertrophy. Conversely, targeting of
endogenous Smad7 by small interfering RNA inhibited C2C12 muscle cell
differentiation, indicating an essential role for Smad7 during
myogenesis. Congruent with a role for Smad7 in myogenesis, we observed
that the muscle regulatory factor (MyoD) binds to and transactivates
the Smad7 proximal promoter region. Finally, we document that Smad7
directly interacts with MyoD and enhances MyoD transcriptional
activity. Thus, Smad7 cooperates with MyoD, creating a positive loop to
induce Smad7 expression and to promote MyoD driven myogenesis. Taken
together, these data implicate Smad7 as a fundamental regulator of
differentiation in skeletal muscle
cells.
MiR-17 and miR-19 cooperatively promote skeletal muscle cell differentiation
