Abstract

Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. The present study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process. A total of 33 rats were divided randomly into control (n=3), mild contusion (n=15), and severe contusion (n=15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n=3 per subgroup). A total of 2844 and 2298 differentially expressed genes (DEGs) were identified using microarray analyses in the mild and severe contusions, respectively. From the analysis of the 1620 coexpressed genes in mildly and severely contused muscle, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. The functional analyses of genes in the functional modules and temporal clusters were performed, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes down-regulated at 24-48 h were largely associated with metabolic processes, especially of the oxidative phosphorylation (OXPHOS), which has been rarely reported. These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

Highlights

  • Muscle trauma frequently occurs in daily life

  • To determine the key mRNAs involved in muscle repair, we used one-way analysis of variance to identify the differentially expressed genes (DEGs) (> 2-fold change, p < 0.05; FDR, < 0.05) among all time points compared to the control group

  • After identifying the downregulated genes associated with oxidative phosphorylation (OXPHOS), we found that they encoded the respiratory chain of complexes I − V (Fig. 6B), which act as electron carriers to generate a proton gradient on both sides of the inner mitochondrial membrane, driving adenosine triphosphate (ATP) synthesis (Fig. 6A) [21, 22]

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Summary

Introduction

Muscle trauma frequently occurs in daily life. the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. Skeletal muscle tissues, which are widely distributed throughout the body, account for 30 − 50% of total body mass [1, 2]. These tissues have a relatively superficial location and are frequently damaged in daily life. Outcomes differ by injury severity: successful repair or inadequate regeneration (fatty degeneration and formation of fibrotic scar tissue) may be observed [9]. These issues emphasize the importance of investigating the cellular response to mechanical muscle damage, to improve treatment of major injuries

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