The response of muscle progenitor cells to cutaneous thermal injury

Yusef Yousuf,Ahmed Shah,Andrea-Kaye Datu,Ali-Reza Sadri,Pantea Samei,Saeid Amini-Nik,Marc G Jeschke

doi:10.1186/s13287-017-0686-z

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.

Highlights

Severe burn results in a systemic response that leads to significant muscle wasting
Pax7 is a transcription factor that regulates the proliferation of these satellite cells; Pax7 is critical for maintaining muscle homeostasis [10, 12]
It is likely that the hypermetabolic response leads to dysregulation of protein degradation and synthesis that plays a role in muscle wasting observed post-burn

Summary

Introduction

Severe burn results in a systemic response that leads to significant muscle wasting. Severe burns result in a sustained inflammatory hypermetabolic response that typically lasts 9–12 months in humans [1, 2] This leads to significant muscle wasting, weakness, and debilitation, which persists for the duration of the hypermetabolic response [1, 3]. There are studies claiming decreased muscle protein synthesis and increased protein degradation after a burn injury [14, 15]. It is likely that the hypermetabolic response leads to dysregulation of protein degradation and synthesis that plays a role in muscle wasting observed post-burn

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