mTor, acting mainly via mTORC1, controls dystrophin transcription in a raptor- and rictor-independent mechanism.

Myostatin, a member of the TGF-beta family, has been identified as a master regulator of embryonic myogenesis and early postnatal skeletal muscle growth. However, cumulative evidence also suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression and that myostatin may contribute to muscle mass loss in adulthood. Two major branches of the Akt pathway are relevant for the regulation of skeletal muscle mass, the Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein degradation. Here, we provide further insights into the mechanisms by which myostatin regulates skeletal muscle mass by showing that myostatin negatively regulates Akt/mTOR signaling pathway. Electrotransfer of a myostatin expression vector into the tibialis anterior muscle of Sprague Dawley male rats increased myostatin protein level and decreased skeletal muscle mass 7 d after gene electrotransfer. Using RT-PCR and immunoblot analyses, we showed that myostatin overexpression was ineffective to alter the ubiquitin-proteasome pathway. By contrast, myostatin acted as a negative regulator of Akt/mTOR pathway. This was supported by data showing that the phosphorylation of Akt on Thr308, tuberous sclerosis complex 2 on Thr1462, ribosomal protein S6 on Ser235/236, and 4E-BP1 on Thr37/46 was attenuated 7 d after myostatin gene electrotransfer. The data support the conclusion that Akt/mTOR signaling is a key target that accounts for myostatin function during muscle atrophy, uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle.

Here, we studied muscle-specific and muscle-related miRNAs in plasma of exercising humans. Our aim was to determine whether they are affected by eccentric and/or concentric exercise modes and could be biomarkers of muscle injuries or possible signaling molecules. On two separate days, nine healthy subjects randomly performed two 30-min walking exercises, one downhill (high eccentric component) and one uphill (high concentric component). Perceived exertion and heart rate were higher during the uphill exercise, while subjective pain and ankle plantar flexor strength losses within the first 48-h were higher following the downhill exercise. Both exercises increased serum creatine kinase and myoglobin with no significant differences between conditions. Plasma levels of circulating miRNAs assessed before, immediately after, and at 2-, 6-, 24-, 48-, and 72-h recovery showed that 1) hsa-mir-1, 133a, 133b, and 208b were not affected by concentric exercise but significantly increased during early recovery of eccentric exercise (2 to 6 h); 2) hsa-mir-181b and 214 significantly and transiently increased immediately after the uphill, but not downhill, exercise. The muscle-specific hsa-mir-206 was not reliably quantified and cardiac-specific hsa-mir-208a remained undetectable. In conclusion, changes in circulating miRNAs were dependent on the exercise mode. Circulating muscle-specific miRNAs primarily responded to a downhill exercise (high eccentric component) and could potentially be alternative biomarkers of muscle damage. Two muscle-related miRNAs primarily responded to an uphill exercise (high exercise intensity), suggesting they could be markers or mediators of physiological adaptations.

MicroRNAs (miRNA) are small non‐coding RNAs that target mRNAs and are consequently involved in the post‐transcriptional regulation of gene expression. Some miRNAs are ubiquitously expressed in tissue, while others are tissue‐specific or tissue‐enriched. miRNAs can be released by cells and are found in various biofluids, including serum and plasma. Thus, measuring miRNAs in the circulation may provide information on the originating tissue or cells. MyomiRs are described as striated muscle‐specific or muscle‐enriched miRNAs. Their circulating levels can be measured and have been proposed to be new biomarkers of physiological and pathological muscle processes. The aims of this review are to summarize the current knowledge of circulating myomiRs, to identify the types of information they can provide about skeletal muscle, and to determine how to apply that information in the fields of research and medicine.