Gene networks in skeletal muscle following endurance exercise are co-expressed in blood neutrophils and linked with blood inflammation markers

It remains incompletely understood whether there is an association between the transcriptome profiles of skeletal muscle and blood leukocytes in response to exercise or other physiological stressors. We have previously analyzed the changes in the muscle and blood neutrophil transcriptome in eight trained men before and 3 h, 48 h and 96 h after 2 h cycling and running. Because we collected muscle and blood in the same individuals and under the same conditions, we were able to directly compare gene expression between the muscle and blood neutrophils. Applying weighted gene co-expression network analysis (WGCNA) as an advanced network-driven method to these original datasets enabled us to compare the muscle and neutrophil transcriptomes in a rigorous and systematic manner. Two gene networks were identified that were preserved between skeletal muscle and blood neutrophils, functionally related to mitochondria and post-translational processes. Strong preservation measures (Zsummary > 10) for both muscle-neutrophil gene networks were evident within the post-exercise recovery period. Muscle and neutrophil gene co-expression was strongly correlated in the mitochondria-related network (r = 0.97; p = 3.17E-2). We also identified multiple correlations between muscular gene sub-networks and exercise-induced changes in blood leukocyte counts, inflammation and muscle damage markers. These data reveal previously unidentified gene co-expression between skeletal muscle and blood neutrophils following exercise, showing the value of WGCNA to understand exercise physiology. Furthermore, these findings provide preliminary evidence in support of the notion that blood neutrophil gene networks may potentially help us to track physiological and pathophysiological changes in the muscle