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Int. J. Mol. Sci. 2017, 18(11), 2488; doi:10.3390/ijms18112488

Extracellular Vesicles Released by Oxidatively Injured or Intact C2C12 Myotubes Promote Distinct Responses Converging toward Myogenesis

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via I Maggetti, 26, 61029 Urbino, Italy
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Received: 18 October 2017 / Revised: 13 November 2017 / Accepted: 19 November 2017 / Published: 22 November 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Myogenic differentiation is triggered, among other situations, in response to muscle damage for regenerative purposes. It has been shown that during myogenic differentiation, myotubes release extracellular vesicles (EVs) which participate in the signalling pattern of the microenvironment. Here we investigated whether EVs released by myotubes exposed or not to mild oxidative stress modulate the behaviour of targeted differentiating myoblasts and macrophages to promote myogenesis. We found that EVs released by oxidatively challenged myotubes (H2O2-EVs) are characterized by an increased loading of nucleic acids, mainly DNA. In addition, incubation of myoblasts with H2O2-EVs resulted in a significant decrease of myotube diameter, myogenin mRNA levels and myosin heavy chain expression along with an upregulation of proliferating cell nuclear antigen: these effects collectively lead to an increase of recipient myoblast proliferation. Notably, the EVs from untreated myotubes induced an opposite trend in myoblasts, that is, a slight pro-differentiation effect. Finally, H2O2-EVs were capable of eliciting an increased interleukin 6 mRNA expression in RAW264.7 macrophages. Notably, this is the first demonstration that myotubes communicate with surrounding macrophages via EV release. Collectively, the data reported herein suggest that myotubes, depending on their conditions, release EVs carrying differential signals which could contribute to finely and coherently orchestrate the muscle regeneration process. View Full-Text
Keywords: exosomes; extracellular vesicles; oxidative stress; myogenic differentiation; intercellular communication; C2C12; H2O2 exosomes; extracellular vesicles; oxidative stress; myogenic differentiation; intercellular communication; C2C12; H2O2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Guescini, M.; Maggio, S.; Ceccaroli, P.; Battistelli, M.; Annibalini, G.; Piccoli, G.; Sestili, P.; Stocchi, V. Extracellular Vesicles Released by Oxidatively Injured or Intact C2C12 Myotubes Promote Distinct Responses Converging toward Myogenesis. Int. J. Mol. Sci. 2017, 18, 2488.

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