Regulation of muscle growth by multiple ligands signaling through activin type II receptors
| Autor: | Man Shiow Jiang, Ronald L. Stotish, Lori A. Reed, En Li, Se-Jin Lee, Monique V. Davies, Li Fang Liang, Mary E.P. Goad, Neil M. Wolfman, Suzanne Sebald, Stefan Girgenrath, Edwin Quattlebaum, Kathy Tomkinson, Jill F. Wright, Gregory Ehrmantraut, James Holmstrom, Christopher M. Barker, Barry Gertz, Betty Trowell, Martin M. Matzuk |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Activin Receptors Type II Myostatin Biology Ligands Muscle hypertrophy Mice Transforming Growth Factor beta Internal medicine medicine Animals Muscle Skeletal Receptor Activin type 2 receptors Mice Knockout Multidisciplinary Organ Size Transforming growth factor beta Activin receptor Biological Sciences musculoskeletal system Endocrinology biology.protein Signal transduction ACVR2B Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:18117-18122 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0505996102 |
| Popis: | 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 . |
| Databáze: | OpenAIRE |
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