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Updated: Oct 13, 2025
Skeletal Muscle Gender Dimorphism from Proteomics
Published on: December 14, 2011
Integrated genomic and proteomic analyses identify stimulus-dependent molecular changes associated with distinct
Liam C Hunt1, Flavia A Graca1, Vishwajeeth Pagala2
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Solid Tumor Program, Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abstract:
Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease, but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer cachexia, and aging) induce largely different mRNA and protein changes during muscle atrophy in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from proteomics as generally induced by atrophy. Rather, we identify proteins that are distinctly modulated by different types of atrophy (herein defined as "atroproteins") such as the myokine CCN1/Cyr61, which regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle atrophy via largely distinct mechanisms.
Insights
Distinct stimuli cause muscle atrophy through different mechanisms, challenging previous models. Proteomics reveals unique "atroproteins" rather than universal markers, highlighting varied molecular pathways in muscle wasting.
Area of Science:
- Molecular biology
- Physiology
- Biochemistry
Background:
- Skeletal muscle atrophy is a significant health issue linked to aging and disease.
- Existing research suggested common transcriptional changes across different atrophy stimuli.
- The proteomic landscape of muscle atrophy remained largely uncharacterized.
Purpose of the Study:
- To investigate whether distinct atrophic stimuli induce similar or different proteomic changes in skeletal muscle.
- To explore the relationship between transcriptome and proteome during muscle atrophy.
- To identify novel protein markers specific to different types of muscle atrophy.
Main Methods:
- Proteomic analysis of mouse skeletal muscle subjected to corticosteroids, cancer cachexia, and aging.
- Transcriptomic analysis for comparison with proteomic data.
- Bioinformatic analysis to identify differentially expressed proteins and mRNAs.
Main Results:
- Distinct stimuli (corticosteroids, cancer cachexia, aging) induced largely different mRNA and protein profiles.
- Significant disconnect observed between transcriptome and proteome during muscle atrophy.
- Previously identified atrophy markers (atrogenes) were not consistently found at the proteome level.
- Novel proteins, termed 'atroproteins,' were identified, with CCN1/Cyr61 highlighted for its role in sarcopenia-related myofiber type switching.
Conclusions:
- Muscle atrophy is driven by diverse molecular mechanisms depending on the catabolic stimulus.
- The transcriptome-proteome disconnect implies complex post-transcriptional regulation in muscle atrophy.
- The identification of specific 'atroproteins' offers new avenues for understanding and potentially targeting muscle wasting conditions.
