Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling

Frontiers in Physiology

卷:8

Francesco Chemello¹  Marcelo G. Pereira²  Leonardo Nogara²  Elena Germinario²  Martina Baraldo²  Vanina Romanello²  Bert Blaauw²  Hendrik Nolte³  Kenneth A. Dyar⁴  Francesca Solagna⁵  Manuela Marabita⁵ 

[1] Department of Biology, University of Padova, Padova, Italy;

[2] Department of Biomedical Sciences, University of Padova, Padova, Italy;

[3] Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany;

[4] Molecular Endocrinology, Institute for Diabetes and Obesity, Helmholtz Diabetes Center and German Center for Diabetes Research, Neuherberg, Germany;

[5] Venetian Institute of Molecular Medicine, Padova, Italy;

关键词: mTORC1;    skeletal muscle;    hypertrophy;    ribosome biogenesis;    immediate early genes;    overload;   

DOI  :  10.3389/fphys.2017.00968

来源: DOAJ

【 摘 要 】

Skeletal muscle mass is a result of the balance between protein breakdown and protein synthesis. It has been shown that multiple conditions of muscle atrophy are characterized by the common regulation of a specific set of genes, termed atrogenes. It is not known whether various models of muscle hypertrophy are similarly regulated by a common transcriptional program. Here, we characterized gene expression changes in three different conditions of muscle growth, examining each condition during acute and chronic phases. Specifically, we compared the transcriptome of Extensor Digitorum Longus (EDL) muscles collected (1) during the rapid phase of postnatal growth at 2 and 4 weeks of age, (2) 24 h or 3 weeks after constitutive activation of AKT, and (3) 24 h or 3 weeks after overload hypertrophy caused by tenotomy of the Tibialis Anterior muscle. We observed an important overlap between significantly regulated genes when comparing each single condition at the two different timepoints. Furthermore, examining the transcriptional changes occurring 24 h after a hypertrophic stimulus, we identify an important role for genes linked to a stress response, despite the absence of muscle damage in the AKT model. However, when we compared all different growth conditions, we did not find a common transcriptional fingerprint. On the other hand, all conditions showed a marked increase in mTORC1 signaling and increased ribosome biogenesis, suggesting that muscle growth is characterized more by translational, than transcriptional regulation.

【 授权许可】

Unknown