Denervation-related alterations and biological activity of miRNAs contained in exosomes released by skeletal muscle fibers
Open accessAbstract
Exosomes are vesicles released by many eukaryotic cells; their cargo includes proteins, mRNA and microRNA (miR) that can be transferred to recipient cells and regulate cellular processes in an autocrine or paracrine manner. While cells of the myoblast lineage secrete exosomes, it is not known whether skeletal muscle fibers (myofibers) release exosomes. In this study, we found that cultured myofibers release nanovesicles that have bilamellar membranes and an average size of 60-130 nm, contain typical exosomal proteins and miRNAs and are taken up by C2C12 cells. miR-133a was found to be the most abundant myomiR in these vesicles while miR-720 was most enriched in exosomes compared to parent myofibers. Treatment of NIH 3T3 cells with myofiber-derived exosomes downregulated the miR-133a targets proteins Smarcd1 and Runx2, confirming that these exosomes have biologically relevant effects on recipient cells. Denervation resulted in a marked increase in miR-206 and reduced expression of miRs 1, 133a, and 133b in myofiber-derived exosomes. These findings demonstrate that skeletal muscle fibers release exosomes which can exert biologically significant effects on recipient cells, and that pathological muscle conditions such as denervation induce alterations in exosomal miR profile which could influence responses to disease states through autocrine or paracrine mechanisms.
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The presence of ELVs was demonstrated in dispersed mouse myofibers from mouse hindlimb muscles.
“and the presence of ELVs was also demonstrated in dispersed mouse myofibers from the mouse hindlimb muscles (De Gasperi et al., 2017).”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as De Gasperi et al., 2017
For the majority of miRNAs, a good correlation was observed between miRNA levels in ELV-MB vs. myoblasts in two independent studies, and between ELVs released from myofibers vs. myofibers.
“For the majority of miRNAs, a good correlation was observed between miRNA levels in ELV-MB vs. MB in two independent studies (Forterre et al., 2014b; Sork et al., 2018), and between ELVs released from myofibers vs. myofibers (De Gasperi et al., 2017)”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as De Gasperi et al., 2017
miR-720 was enriched in myofiber-derived ELVs compared with parent myofibers, and inversely for miR-1.
“Similarly, miR-720 was enriched in myofiber-derived ELVs compared with parent myofibers and inversely for miR-1 (De Gasperi et al., 2017).”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as De Gasperi et al., 2017
After denervation, muscle fibers release a new population of ELVs enriched in miR-206 able to downregulate Smarcd1 and Runx2 proteins in NIH3T3 adipocytes.
“after denervation, muscle fiber released a new population of ELVs enriched in miR-206 able to downregulate the expression of Smarcd1 and Runx2 proteins into NIH3T3 adipocytes”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as De Gasperi et al., 2017
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Skeletal Muscle-Released Extracellular Vesicles: State of the Art
Rome, S., Forterre, A., Mizgier, M. L., & Bouzakri, K. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00929 · Cited by 139 · see citing works
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- Authors
- De Gasperi, R., Hamidi, S., Harlow, L. M., Ksiezak-Reding, H., Bauman, W. A., & Cardozo, C. P.
- Affiliations
- James J. Peters VA Medical Center (US)
- Corresponding author
- Cardozo, Christopher P.
- Venue
- Scientific Reports
- Published
- 2017-10-16
- Volume
- 7
- Issue
- 1
- Pages
- 12888-12888
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5643439
- OpenAlex
- W2763595865
- Cited by
- 75
- References
- 58
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 8 · 2021: 13 · 2020: 8 · 2019: 13 · 2018: 2
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Rehabilitation Research and Development Service
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- exosomes, skeletal muscle fibers, microRNA, denervation, miR-133a, miR-206, myomiRs, exosomal cargo, SMARCD1, Runx2, autocrine and paracrine signaling, muscle atrophy, C2C12 myoblasts, NIH3T3 cells
- MeSH terms
- Animals, Cells, Cultured, Chromosomal Proteins, Non-Histone, Denervation, Gene Expression Regulation, Male, Mice, Inbred C57BL, RNA, Messenger, Down-Regulation, Muscle Fibers, Skeletal, Myoblasts, MicroRNAs, NIH 3T3 Cells, Core Binding Factor Alpha 1 Subunit, Mice, Nanoparticles, Exosomes
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