AUTHOR=Hagg Adam , Kharoud Swati , Goodchild Georgia , Goodman Craig A. , Chen Justin L. , Thomson Rachel E. , Qian Hongwei , Gregorevic Paul , Harrison Craig A. , Walton Kelly L. TITLE=TMEPAI/PMEPA1 Is a Positive Regulator of Skeletal Muscle Mass JOURNAL=Frontiers in Physiology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.560225 DOI=10.3389/fphys.2020.560225 ISSN=1664-042X ABSTRACT=
Inhibition of myostatin- and activin-mediated SMAD2/3 signaling using ligand traps, such as soluble receptors, ligand-targeting propeptides and antibodies, or follistatin can increase skeletal muscle mass in healthy mice and ameliorate wasting in models of cancer cachexia and muscular dystrophy. However, clinical translation of these extracellular approaches targeting myostatin and activin has been hindered by the challenges of achieving efficacy without potential effects in other tissues. Toward the goal of developing tissue-specific myostatin/activin interventions, we explored the ability of transmembrane prostate androgen-induced (TMEPAI), an inhibitor of transforming growth factor-β (TGF-β1)-mediated SMAD2/3 signaling, to promote growth, and counter atrophy, in skeletal muscle. In this study, we show that TMEPAI can block activin A, activin B, myostatin and GDF-11 activity