Roles of exosome-like vesicles released from inflammatory C2C12 myotubes: regulation of myocyte differentiation and myokine expression
Open accessAbstract
BACKGROUND/AIMS: The complicated differentiation processes of cells in skeletal muscle against inflammation that induce muscle atrophy are not fully elucidated. Given that skeletal muscle is a secretory organ, we evaluated the effects of inflammation on myogenic signals and myokine expression, and the roles of inflammatory exosomes released by myotubes in myogenic differentiation. METHODS: Inflammation was induced by treatment of fully differentiated C2C12 myotubes with a cytokine mixture of TNF-α and INF-γ. Exosome-like vesicles (ELVs) were isolated from conditioned media of control or inflamed myotubes and incubated with myoblasts. The expression of molecular switches that contribute to myogenic differentiation, including several kinases, their downstream targets, and myokines, were evaluated using immunoblot analysis in inflamed myotubes and in myoblasts treated with ELVs. RESULTS: Inflammation activated molecular mechanisms contributing to muscle atrophy, including AMPK, p-38 MAPK and JNK, while inhibiting Akt-mediated myogenic signals. In addition, inflammation induced myostatin expression with suppression of a myostatin-counteracting myokine, decorin. Well-characterized ELVs released from inflamed myotubes induced myoblast inflammation and inhibited myogenic mechanisms while stimulating atrophic signals. CONCLUSION: Inflammation of skeletal muscle induces muscle atrophy via multiple mechanisms, including the regulation of myokines and kinases. Inflammatory ELVs are likely to contribute to inflammation-induced muscle atrophy.
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ELV-MT participate in the maintenance and regeneration of SkM mass following injuries.
“suggesting that in addition to myogenesis, ELV-MT would also participate in the maintenance and regeneration of SkM mass following injuries.”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Kim et al., 2018
Similar results are obtained when myotubes are treated with a pro-inflammatory cytokine mixture of TNF-alpha and INF-gamma.
“Similar results were obtained when myotubes were treated with a pro-inflammatory cytokine mixture of TNF-alpha and INF-gamma”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Kim et al., 2018
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Idiopathic inflammatory myopathy and non-coding RNA
Yang, Y., GuangXuan, H., GenMeng, W., Li, M., Chang, B., & Yi, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1227945 · Cited by 5 · see citing works
“miR-223 Up IKK-a Neutrophils/ macrophages Muscle injury Mice Inflammation RT-PCR (46, 47)”
Myokines: A potential key factor in development, treatment, and biomarker of sarcopenia
Aoi, W. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00006-5 · Cited by 4 · see citing works
Li, Z., Hou, D., Tang, Z., Xiong, L., & Yan, Y. (2023) · Cell Biology International · doi:10.1002/cbin.12107 · Cited by 2 · see citing works
“…levels of myogenic determinants and myopoietin by carrying myogenic inhibitory proteins, as well as by myogenic signaling pathways mediated by protein kinase B and rapamycin target proteins, and they also increase the expression level of cyclooxygenase ‐ 2 in myoblasts (Kim et al., 2018).”
BackgroundSkeletal Muscle–Extricated Extracellular Vesicles: Facilitators of Repair and Regeneration
Yedigaryan, L., & Sampaolesi, M. (2022) · Springer eBooks · doi:10.1007/978-981-19-2655-6_49 · Cited by 1 · see citing works
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Skeletal muscle mitochondrial clearance
Leermakers (2019) · doi:10.26481/dis.20190405pl
Skeletal Muscle–Extricated Extracellular Vesicles: Facilitators of Repair and Regeneration
Yedigaryan, L., & Sampaolesi, M. (2022) · Springer eBooks · doi:10.1007/978-981-16-6016-0_49-1
Regulation of Metabolism and Exercise Functions Associated with Skeletal Muscle and Gut Crosstalk
Aoi, W. (2023) · Nippon Eiyo Shokuryo Gakkaishi · doi:10.4327/jsnfs.76.305
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“EVs collected from myotubes cultured under inflammatory con - ditions inhibited myoblast differentiation to myotubes (Kim et al. 2018 ).”
InfluentialPan, Q., Lou, M., Zhu, M., et al. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.152258
- Authors
- Kim, S., Lee, M.-J., Choi, J.-Y., Park, D.-H., Kwak, H.-B., Moon, S., Koh, J.-W., Shin, H.-K., Ryu, J.-K., Park, C.-S., Park, J. H., & Kang, J.-H.
- Affiliations
- Inha University (KR)
- Kangbuk Samsung Hospital (KR)
- ORCID
- Venue
- Cellular Physiology and Biochemistry
- Publisher
- S. Karger AG
- Published
- 2018
- Volume
- 48
- Issue
- 5
- Pages
- 1829-1842
- ISSN
- 1015-8987 (ISSN-L)
- 1421-9778
- OpenAlex
- W2885125141
- Cited by
- 44
- References
- 52
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 9 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular Physiology and Biochemistry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- exosome-like nanoparticles, skeletal muscle inflammation, muscle atrophy, myogenesis, myokines, myostatin, decorin, TNF-α, interferon-gamma, AMPK, p38 MAPK, JNK, Akt signaling, C2C12 myotubes, myoblasts, extracellular vesicles
- MeSH terms
- Autophagy-Related Proteins, Animals, Cell Differentiation, Cell Line, Gene Expression Regulation, Phosphorylation, Signal Transduction, Cytokines, MyoD Protein, Myogenin, Muscle Fibers, Skeletal, Myoblasts, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Mice, Cell-Derived Microparticles, AMP-Activated Protein Kinases, Myostatin, Decorin
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