Evaluating the Effects of Systemic, Exercise-Induced Skeletal Muscle Injury using Whole Transcriptome Sequencing

Abstract

Recent advances in next generation sequencing have dramatically reduced the cost of whole transcriptome sequencing to measure differential gene expression. Extreme physical performances represent a unique model for investigating the combined effects of oxidative stress and eccentric muscle contraction on systemic skeletal muscle injury outcomes. Studying changes in whole transcriptome RNA expression may allow identification of specific potential treatment targets for a variety of disease states associated with chronic inflammation and oxidative stress. The purpose of this study was to investigate changes in whole transcriptome RNA expression in response to prolonged endurance running. The protocols were approved by the University IRB committee (in accordance with the latest Declaration of Helsinki) and subjects gave written informed consent to participate. Blood samples were collected in PAXgene RNA tubes at baseline, 4-h, and 24-h after performing a half-marathon race. After collection, tubes were frozen and total RNA was extracted and verified using accepted methods. RNAseq analysis was conducted using an Illumina NextSeq 500 sequencing platform. RNAseq analysis revealed distinct changes in injury, inflammation, anti-oxidant defense, and stress-associated RNA expression with responses appearing more pronounced at 24-h compared to 4-h post-race. These results confirm the systemic changes that occur following whole-body exercise-induced muscle injury in a human model. The next step in this research is to test potential therapeutic strategies to determine their effectiveness on altering the changes in the transcriptome.