Dynamics of the skeletal muscle secretome during myoblast differentiation
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During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics of protein secretion. We identified and quantitatively analyzed 635 secreted proteins, including 35 growth factors, 40 cytokines, and 36 metallopeptidases. The extensive presence of these proteins that can act as potent signaling mediators to other cells and tissues strongly highlights the important role of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188 of these secreted proteins to be significantly regulated during the process of myogenesis. Comparative analyses of selected secreted proteins revealed little correlation between their mRNA and protein levels, indicating pronounced regulation by posttranscriptional mechanisms. Furthermore, analyses of the intracellular levels of members of the semaphorin family and their corresponding secretion dynamics demonstrated that the release of secreted proteins is tightly regulated by the secretory pathway, the stability of the protein, and/or the processing of secreted proteins. Finally, we provide 299 unique hydroxyproline sites mapping to 48 distinct secreted proteins and have discovered a novel hydroxyproline motif.
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Myokines are involved in muscle proliferation, differentiation, and regeneration independent of exercise.
“Myokines are also involved in muscle proliferation, differentiation, and regeneration independent of exercise (39, 40).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [40]
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- Authors
- Henningsen, J., Rigbolt, K. T. G., Blagoev, B., Pedersen, B. K., & Kratchmarova, I.
- Affiliations
- University of Southern Denmark (DK)
- University of Copenhagen (DK)
- Corresponding author
- Kratchmarova, Irina
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 9
- Issue
- 11
- Pages
- 2482-2496
- ISSN
- 1535-9476 (ISSN-L)
- PMC
- PMC2984231
- OpenAlex
- W2118550160
- Cited by
- 303
- References
- 78
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 14 · 2023: 22 · 2022: 12 · 2021: 16 · 2020: 23 · 2019: 21 · 2018: 19 · 2017: 24 · 2016: 17 · 2015: 30 · 2014: 33 · 2013: 28 · 2012: 20
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular & Cellular Proteomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- National Research Foundation
- Danmarks Grundforskningsfond
- Lundbeckfonden
- Novo Nordisk
- Novo Nordisk Fonden
- H. Lundbeck A/S
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- myogenesis, secreted proteins, C2C12 myoblasts, growth factors, cytokines, metalloproteinases, semaphorins, post-transcriptional regulation, paracrine signaling
- MeSH terms
- Amino Acid Sequence, Animals, Cell Differentiation, Cell Line, Isotope Labeling, Molecular Sequence Data, Muscle Proteins, Mass Spectrometry, Muscle, Skeletal, Protein Isoforms, Myoblasts, Semaphorins, Proteomics, Mice
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