Résumé :
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Myostatin, a member of the TGF-_ superfamily of ligands, has been shown to be a negative regulator of skeletal muscle mass during embryogenesis and early postnatal muscle growth. Several studies indicate that myostatin is an important mediator of muscle atrophy. Evidence has strongly suggested that hypoxia can also induce muscle atrophy. Hypoxia can be caused by a generalized reduction in oxygen delivery, such as altitude and pulmonary diseases, or by disruption in the local blood supply, such as an ischemic disorder. So, we know that myostatin and hypoxia signaling pathways are able to induce skeletal muscle atrophy, but whether a relationship between these two pathways exists is currently unknown. Here, we tested the hypothesis that a potential mechanism for hypoxia effect on skeletal muscle may be through regulation of myostatin. We reported an induction of myostatin expression in muscles of rats exposed to chronic hypoxia. Interestingly, we also demonstrated increased skeletal muscle myostatin protein expression in skeletal muscle of hypoxemic patients with severe chronic obstructive pulmonary disease (COPD). Parallel studies in human skeletal muscle cell cultures showed that induction of myostatin expression in myotubes treated with hypoxia-mimicking agent such as cobalt chloride (CoCl2) is associated with myotube atrophy. Furthermore, we demonstrated that inhibition of myostatin by means of genetic deletion of myostatin or treatment with blocking antimyostatin antibodies inhibits the CoCl2-induced atrophy in muscle cells. Finally, addition of recombinant myostatin restored the CoCl2 induced atrophy in myostatin deficient myotubes. These results strongly suggest that myostatin can play an essential role in the adaptation of skeletal muscle to hypoxic environment
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