LAUSR

Skeletal muscle is adaptable to a direct stimulus of exercise-induced muscle damage (EIMD). Local muscle gene networks and systemic circulatory factors respond to EIMD within days, mediating anti-inflammation and cellular proliferation. Here we show in humans that local EIMD of one muscle group is associated with a systemic response of gene networks that regulate muscle structure and cellular development in non-local homologous muscle not directly altered by EIMD. In the non-dominant knee-extensors of seven males, EIMD was induced through voluntary contractions against an electric motor that lengthened muscles. Neuromuscular assessments, vastus lateralis muscle biopsies and blood draws occurred at two days prior, and one and two days post the EIMD intervention. From the muscle and blood plasma samples, RNA-seq measured transcriptome changes of differential expression using bioinformatic analyses.Relative to the time of the EIMD intervention, local muscle that was mechanically damaged had 475 genes differentially expressed, as compared to 33 genes in the non-local homologous muscle. Gene and network analysis showed that activity of the local muscle was related to structural maintenance, repair, and energetic processes, whereas gene and network activity of the non-local muscle (that was not directly modified by the EIMD) were related to muscle cell development, stress response, and structural maintenance. Altered expression of two novel miRNAs related to the EIMD response supported that systemic factors were active. Together, these results indicate that the expression of genes and gene networks that control muscle contractile structure can be modified in response to non-local EIMD in humans.