期刊
JOURNAL OF CELL BIOLOGY
卷 203, 期 2, 页码 345-357出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201211134
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资金
- National Health and Medical Research Council (NHMRC) of Australia [526648, 1008910, 1006488]
- Motor Neuron Disease Research Institute of Australia Mick Rodger Motor Neuron Disease research grant
- Swedish Foundation for International Cooperation in Research and Higher Education
- NHMRC [1013533, 1030474, 1046782]
- Australian Research Council [FT0001657]
- Honorary Senior Research Fellowship from the NHMRC [586604]
- Pfizer Australia
- Operational Infrastructure Support Program of the Victorian Government
Although the canonical transforming growth factor. signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin-dependent process, whereas increased BMP-Smad1/5 activity protected muscles from denervation- induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.
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