期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 50, 页码 18117-18122出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0505996102
关键词
myostatin; TGF-beta
资金
- NCI NIH HHS [R01 CA088866, R01CA88866] Funding Source: Medline
- NICHD NIH HHS [R01HD32067, R01 HD035887, R01HD35887, R01 HD032067] Funding Source: Medline
Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn(-/-) mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.
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