The response of muscle progenitor cells to cutaneous thermal injury

Abstract

BackgroundSevere burn results in a systemic response that leads to significant muscle wasting. It is believed that this rapid loss in muscle mass occurs due to increased protein degradation combined with reduced protein synthesis. Alterations in the microenvironment of muscle progenitor cells may partially account for this pathology. The aim of this study was to ascertain the response of muscle progenitor cells following thermal injury in mice and to enlighten the cellular cascades that contribute to the muscle wasting.MethodsC57BL/6 mice received a 20% total body surface area (TBSA) thermal injury. Gastrocnemius muscle was harvested at days 2, 7, and 14 following injury for protein and histological analysis.ResultsWe observed a decrease in myofiber cross-sectional area at 2 days post-burn. This muscle atrophy was compensated for by an increase in myofiber cross-sectional area at 7 and 14 days post-burn. Myeloperoxidase (MPO)-positive cells (neutrophils) increased significantly at 2 days. Moreover, through Western blot analysis of two key mediators of the proteolytic pathway, we show there is an increase in Murf1 and NF-κB 2 days post-burn. MPO-positive cells were also positive for NF-κB, suggesting that neutrophils attain NF-κB activity in the muscle. Unlike inflammatory and proteolytic pathways, the number of Pax7-positive muscle progenitor cells decreased significantly 2 days post-burn. This was followed by a recovery in the number of Pax7-positive cells at 7 and 14 days, suggesting proliferation of muscle progenitors that accompanied regrowth.ConclusionOur data show a biphasic response in the muscles of mice exposed to burn injury, with phenotypic characteristics of muscle atrophy at 2 days while compensation was observed later with a change in Pax7-positive muscle progenitor cells. Targeting muscle progenitors may be of therapeutic benefit in muscle wasting observed after burn injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0686-z) contains supplementary material, which is available to authorized users.

Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells

“…Protein expression of Pax7 in the burn group was significantly reduced in the muscle at 7 days post-thermal injury when compared with sham and metformin groups, which is in line with our previous report (Fig. 5a, b) [37]. Interestingly, metformin significantly increased protein expression of Pax7 compared to sham and burn groups (Fig.…”

“…Activation of NF-κB results in the transcription of muscle-specific ubiquitin ligases such as MurF1 that cause protein degradation [58,59]. Furthermore, NF-κB p65 has been shown to be elevated in the skeletal muscle of mice [37] and in the serum of burn patients [60]. We observed a significant increase in NF-κB p65 protein level and the number of NF-κB p65-positive myonuclei after severe burn injury (Fig.…”

“…To characterize metformin's mechanisms in mitigating burn-induced muscle wasting, and with the consideration that our latest report revealed temporal changes in Pax7- positive muscle progenitor cells post-thermal injury [37], we examined how satellite cells responded to metformin treatment. Metformin treatment significantly increased the number of muscle progenitors (Pax7 + ) and the protein level of Pax7 when compared with sham and burned animals ( Fig.…”

“…Satellite cells are essential for skeletal muscle regeneration following injury [32] and for muscle hypertrophy and homeostasis [33][34][35]. Recent reports have illustrated a reduction in satellite cell numbers and an increase in myonuclear apoptosis post-burn injury in both humans and mice [36,37]. Dysregulation of satellite cells may impair their ability to repair skeletal muscle after thermal injury.…”

Biological characteristics of stem cells derived from burned skin—a comparative study with umbilical cord stem cells

“…We do not know how long our samples were exposed to the burn; however, a scalding exposure usually occurs within seconds. This avenue needs to be further explored due to the complexity of cell damage [ 44 ] and to be able to make adequate comparisons [ 45 ] in BD-MSCs.…”