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

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1998-2008
Number of pages11
JournalMolecular Endocrinology
Volume24
Issue number10
DOIs
Publication statusPublished - 01-10-2010

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Follistatin
Activins
Myostatin
Muscles
Cardiotoxins
Haploinsufficiency
Muscular Atrophy
Muscle Development
Heterozygote
Carrier Proteins
Skeletal Muscle
Maintenance
Parturition
Ligands
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Lee, S. J., Lee, Y. S., Zimmers, T. A., Soleimani, A., Matzuk, M. M., Tsuchida, K., ... 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
Lee, Se Jin ; Lee, Yun Sil ; Zimmers, Teresa A. ; Soleimani, Arshia ; Matzuk, Martin M. ; Tsuchida, Kunihiro ; Cohn, Ronald D. ; Barton, Elisabeth R. / Regulation of muscle mass by follistatin and activins. In: Molecular Endocrinology. 2010 ; Vol. 24, No. 10. pp. 1998-2008.
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Lee, SJ, Lee, YS, Zimmers, TA, Soleimani, A, Matzuk, MM, Tsuchida, K, Cohn, RD & Barton, ER 2010, 'Regulation of muscle mass by follistatin and activins', Molecular Endocrinology, vol. 24, no. 10, pp. 1998-2008. https://doi.org/10.1210/me.2010-0127

Regulation of muscle mass by follistatin and activins. / Lee, Se Jin; Lee, Yun Sil; Zimmers, Teresa A.; Soleimani, Arshia; Matzuk, Martin M.; Tsuchida, Kunihiro; Cohn, Ronald D.; Barton, Elisabeth R.

In: Molecular Endocrinology, Vol. 24, No. 10, 01.10.2010, p. 1998-2008.

Research output: Contribution to journalArticle

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Lee SJ, Lee YS, Zimmers TA, Soleimani A, Matzuk MM, Tsuchida K et al. Regulation of muscle mass by follistatin and activins. Molecular Endocrinology. 2010 Oct 1;24(10):1998-2008. https://doi.org/10.1210/me.2010-0127