Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling
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 hype...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-12-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00968/full |
| _version_ | 1819142036762132480 |
|---|---|
| author | Marcelo G. Pereira Marcelo G. Pereira Kenneth A. Dyar Kenneth A. Dyar Leonardo Nogara Leonardo Nogara Francesca Solagna Manuela Marabita Martina Baraldo Martina Baraldo Francesco Chemello Elena Germinario Vanina Romanello Vanina Romanello Hendrik Nolte Bert Blaauw Bert Blaauw |
| author_facet | Marcelo G. Pereira Marcelo G. Pereira Kenneth A. Dyar Kenneth A. Dyar Leonardo Nogara Leonardo Nogara Francesca Solagna Manuela Marabita Martina Baraldo Martina Baraldo Francesco Chemello Elena Germinario Vanina Romanello Vanina Romanello Hendrik Nolte Bert Blaauw Bert Blaauw |
| author_sort | Marcelo G. Pereira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T12:03:58Z |
| format | Article |
| id | doaj.art-3fac33da69a24111a4d639bbbfaff226 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-22T12:03:58Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-3fac33da69a24111a4d639bbbfaff2262022-12-21T18:26:29ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-12-01810.3389/fphys.2017.00968309717Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR SignalingMarcelo G. Pereira0Marcelo G. Pereira1Kenneth A. Dyar2Kenneth A. Dyar3Leonardo Nogara4Leonardo Nogara5Francesca Solagna6Manuela Marabita7Martina Baraldo8Martina Baraldo9Francesco Chemello10Elena Germinario11Vanina Romanello12Vanina Romanello13Hendrik Nolte14Bert Blaauw15Bert Blaauw16Venetian Institute of Molecular Medicine, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyVenetian Institute of Molecular Medicine, Padova, ItalyMolecular Endocrinology, Institute for Diabetes and Obesity, Helmholtz Diabetes Center and German Center for Diabetes Research, Neuherberg, GermanyVenetian Institute of Molecular Medicine, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyVenetian Institute of Molecular Medicine, Padova, ItalyVenetian Institute of Molecular Medicine, Padova, ItalyVenetian Institute of Molecular Medicine, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyDepartment of Biology, University of Padova, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyVenetian Institute of Molecular Medicine, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyInstitute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, GermanyVenetian Institute of Molecular Medicine, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalySkeletal 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.http://journal.frontiersin.org/article/10.3389/fphys.2017.00968/fullmTORC1skeletal musclehypertrophyribosome biogenesisimmediate early genesoverload |
| spellingShingle | Marcelo G. Pereira Marcelo G. Pereira Kenneth A. Dyar Kenneth A. Dyar Leonardo Nogara Leonardo Nogara Francesca Solagna Manuela Marabita Martina Baraldo Martina Baraldo Francesco Chemello Elena Germinario Vanina Romanello Vanina Romanello Hendrik Nolte Bert Blaauw Bert Blaauw 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 mTORC1 skeletal muscle hypertrophy ribosome biogenesis immediate early genes overload |
| title | Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling |
| title_full | Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling |
| title_fullStr | Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling |
| title_full_unstemmed | Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling |
| title_short | Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling |
| title_sort | comparative analysis of muscle hypertrophy models reveals divergent gene transcription profiles and points to translational regulation of muscle growth through increased mtor signaling |
| topic | mTORC1 skeletal muscle hypertrophy ribosome biogenesis immediate early genes overload |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00968/full |
| work_keys_str_mv | AT marcelogpereira comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT marcelogpereira comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT kennethadyar comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT kennethadyar comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT leonardonogara comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT leonardonogara comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT francescasolagna comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT manuelamarabita comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT martinabaraldo comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT martinabaraldo comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT francescochemello comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT elenagerminario comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT vaninaromanello comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT vaninaromanello comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT hendriknolte comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT bertblaauw comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling AT bertblaauw comparativeanalysisofmusclehypertrophymodelsrevealsdivergentgenetranscriptionprofilesandpointstotranslationalregulationofmusclegrowththroughincreasedmtorsignaling |