Regulation of muscle mass by follistatin and activins

Se Jin Lee, Yun Sil Lee, Teresa A. Zimmers, Arshia Soleimani, Martin M. Matzuk, Kunihiro Tsuchida, Ronald D. Cohn, Elisabeth R. Barton

研究成果: Article

147 引用 (Scopus)

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Myostatin is a TGF-β family member that normally acts to limit skeletal muscle mass. Follistatin is a myostatin-binding protein that can inhibit myostatin activity in vitro and promote muscle growth in vivo. Mice homozygous for a mutation in the Fst gene have been shown to die immediately after birth but have a reduced amount of muscle tissue, consistent with a role for follistatin in regulating myogenesis. Here, we show that Fst mutant mice exhibit haploinsufficiency, with muscles of Fst heterozygotes having significantly reduced size, a shift toward more oxidative fiber types, an impairment of muscle remodeling in response to cardiotoxin-induced injury, and a reduction in tetanic force production yet a maintenance of specific force. We show that the effect of heterozygous loss of Fst is at least partially retained in a Mstn-null background, implying that follistatin normally acts to inhibit other TGF-β family members in addition to myostatin to regulate muscle size. Finally, we present genetic evidence suggesting that activin A may be one of the ligands that is regulated by follistatin and that functions with myostatin to limit muscle mass. These findings potentially have important implications with respect to the development of therapeutics targeting this signaling pathway to preserve muscle mass and prevent muscle atrophy in a variety of inherited and acquired forms of muscle degeneration.

元の言語English
ページ(範囲)1998-2008
ページ数11
ジャーナルMolecular Endocrinology
24
発行部数10
DOI
出版物ステータスPublished - 01-10-2010

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

これを引用

Lee, S. J., Lee, Y. S., Zimmers, T. A., Soleimani, A., Matzuk, M. M., Tsuchida, K., Cohn, R. D., & Barton, E. R. (2010). Regulation of muscle mass by follistatin and activins. Molecular Endocrinology, 24(10), 1998-2008. https://doi.org/10.1210/me.2010-0127