Journal article
Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin
CE Winbanks, KL Weeks, RE Thomson, PV Sepulveda, C Beyer, H Qian, JL Chen, AM Allen, GI Lancaster, MA Febbraio, CA Harrison, JR McMullen, JS Chamberlain, P Gregorevic
Journal of Cell Biology | Published : 2012
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 on..
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Awarded by National Institute on Aging
Funding Acknowledgements
This work was supported by funding from the National Health and Medical Research Council (NHMRC; Australia) awarded to P. Gregorevic (526648), and C.A. Harrison (1006488), from the Muscular Dystrophy Association (USA) awarded to P. Gregorevic (69684), and funding from the National Institutes of Health (AG033610) awarded to J.S. Chamberlain. M.A. Febbraio is supported by an NHMRC Senior Principal Research Fellowship. C.A. Harrison is supported by a NHMRC Career Development Fellowship (1013533). J.R. McMullen is supported by an Australian Research Council Future Fellowship (FT0001657) and Honorary NHMRC Senior Research Fellowship (586604). P. Gregorevic is supported by a Senior Research Fellowship sponsored by Pfizer Australia. The Baker IDI Heart and Diabetes Institute is supported in part by the Operational Infrastructure Support Program of the Victorian Government.