Regulation of muscle growth by multiple ligands signaling through activin type II receptors

Se Jin Lee, Lori A. Reed, Monique V. Davies, Stefan Girgenrath, Mary E.P. Goad, Kathy N. Tomkinson, Jill F. Wright, Christopher Barker, Gregory Ehrmantraut, James Holmstrom, Betty Trowell, Barry Gertz, Man Shiow Jiang, Suzanne M. Sebald, Martin Matzuk, En Li, Li Fang Liang, Edwin Quattlebaum, Ronald L. Stotish, Neil M. Wolfman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18117-18122
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number50
DOIs
StatePublished - Dec 13 2005

Keywords

  • Myostatin
  • TGF-β

ASJC Scopus subject areas

  • General

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