Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin.

ABSTRACT: Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed fol

SUBMITTER: Winbanks CE 

PROVIDER: S-EPMC3384410 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature