Published online Nov 26, 2021. doi: 10.4252/wjsc.v13.i11.1762
Peer-review started: May 1, 2021
First decision: June 16, 2021
Revised: June 28, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: November 26, 2021
Processing time: 207 Days and 22.1 Hours
More than half of sports injuries in athletes have been reported to be related to muscle damage. Severely injured muscles are prone to re-injury due to fibrotic scar formation caused by prolonged inflammation. How to regulate inflammation and suppress fibrosis is the focus of promoting muscle healing.
Recent studies have found that myoblasts and macrophages play important roles in the inflammatory phase following muscle injury; however, the crosstalk between these two types of cells in the inflammatory environment, particularly the exosome-related mechanisms, has not been well studied.
This study aimed to evaluate the effects of exosomes from inflammatory C2C12 myoblasts (IF-C2C12-Exos) on macrophage polarization and myoblast proliferation/ differentiation.
A model of inflammation was established in vitro by lipopolysaccharide stimulation of myoblasts. Multiple methods were used to isolate and identify the exosomes. Gradient concentrations of IF-C2C12-Exos were added to normal macrophages and myoblasts. PKH67 fluorescence tracing, microscopic morphology, Giemsa staining, immunofluorescence, ELISA assays, flow cytometry, western blot, BrdU test, scratch assay, and CCK-8 assay were conducted to determine the mechanism of IF-C2C12-Exos.
We found that the PKH-67-marked C2C12-Exos can be endocytosed by both macr
IF-C2C12-Exos can induce M1 polarization, resulting in a sustained and aggravated inflammatory environment that impairs myoblast differentiation, and leads to enhanced myogenic proliferation. These results demonstrate why prolonged inflammation occurs after acute muscle injury and provide a new target for the regulation of muscle regeneration.
Given the pathophysiological significance of the findings of this study, further studies are needed to elucidate the mechanisms responsible for these effects which deserve investigation. It is hoped that further studies will identify specific targets involved in muscle regeneration and fibrosis, such as lncRNAs and miRNAs.