Quantitative analysis of the secretion of the MCP family of chemokines by muscle cells
Abstract
The plasticity of skeletal muscle allows the body to adapt to various physiological demands such as growth, exercise and tissue regeneration and repair. The secreted factors from muscle exert their action via auto-, para-, and endocrine mechanisms, thereby influencing the maintenance of total body homeostasis. In addition, the regulation of muscle proliferation, differentiation, and regeneration is often perturbed by inflammatory processes and is dependent on the pattern of expression of pro-inflammatory stimuli. Studies examining the cross talk between factors released by muscle and cytokines secreted by other tissues are still very limited. In order to comprehensively characterize the low abundant low molecular weight secreted proteins during the course of muscle differentiation we used a mass spectrometry-based proteomics strategy. The application of the triple encoding Stable Isotope Labeling by Amino acids in Cell culture (SILAC) method for quantitative analysis resulted in the identification and generation of quantitative profiles of 59 growth factors and cytokines, including 9 classical chemokines. The members of the CC chemokine family of proteins such as monocyte chemotactic proteins 1, 2, and 3 (MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7) showed a distinct pattern of secretion during differentiation. Further analysis using combinatorial RNA and protein approaches demonstrated that the MCPs are regulated via both post-transcriptional and post-translational mechanisms. Analyses of the autocrine function of all three MCPs reveal similar activation of downstream effectors in muscle cells. Finally, we show that the expression of the MCPs in skeletal muscle is also regulated by pro-inflammatory stimuli, indicating a much broader cross talk and interaction between inflammatory-dependent systems than previously anticipated.
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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 [39]
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“Attenuated expression of the chemokine CCL8 (Henningsen et al. 2011) and the secreted regenerative marker SPARC (Jorgensen et al.”
InfluentialRNAi Screen Reveals Potentially Novel Roles of Cytokines in Myoblast Differentiation
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“Recent proteomic analyses of the secretome of the myogenic C2C12 cells have revealed tens of cytokines and growth factors that are expressed during differentiation in a regulated manner [20,21].”
BackgroundUnderstanding regeneration through proteomics
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Combining Pulsed SILAC Labeling and Click-Chemistry for Quantitative Secretome Analysis
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“The large number of chemokines and chemokine receptors directly expressed by muscle cells suggests that these proteins, and their immunological functions, might have a greater role in myogenesis or muscle regeneration than previously appreciated [60–64].”
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“Secretome studies show that myoblasts secrete different factors during proliferation than during differentiation, and even at different time points throughout differentiation.(8,10,11) Another study identified numerous chemokine mRNAs expressed by differentiating myoblasts, which may be involved in regulating cell mig…”
BackgroundExerkines and myokines in aging sarcopenia
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Quantitative Proteomics for Investigation of Secreted Factors: Focus on Muscle Secretome
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“…characterization of the low abundant low molecular weight fraction of proteins secreted by muscle cells, application of triple encoding SILAC resulted in the generation of quantitative profiles of 59 growth factors and cytokines, including nine classical chemokines (Henningsen et al., 2011).”
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“The source of plasma cytokines in patients with ME/CFS are unclear, but a number of cytokines can be produced by muscle (75-78).”
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Hsp60 and skeletal muscle diseases
Barone, R., Cappello, F., de Macario, E. C., & Macario, A. J. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23996-0.00007-9
- Authors
- Henningsen, J., Pedersen, B. K., & Kratchmarova, I.
- Affiliations
- University of Southern Denmark (DK)
- University of Copenhagen (DK)
- Corresponding author
- Kratchmarova, Irina
- Venue
- Molecular BioSystems
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12-08
- Volume
- 7
- Issue
- 2
- Pages
- 311-321
- ISSN
- 1742-2051 (ISSN-L)
- 1742-206X
- OpenAlex
- W1987872632
- Cited by
- 51
- References
- 62
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 8 · 2014: 4 · 2013: 7 · 2012: 5
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular BioSystems (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Danmarks Grundforskningsfond
- Lundbeckfonden
- Augustinus Fonden
- Novo Nordisk Fonden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- monocyte chemoattractant protein, CCL2/MCP-1, CC chemokines, skeletal muscle differentiation, secreted proteins, cytokines and growth factors, autocrine signaling, post-transcriptional regulation, post-translational regulation, pro-inflammatory stimuli, muscle inflammation, muscle regeneration
- MeSH terms
- Cell Differentiation, Humans, Protein Processing, Post-Translational, RNA, Messenger, Culture Media, Conditioned, Muscle, Skeletal, Monocyte Chemoattractant Proteins, Tandem Mass Spectrometry
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