Small noncoding
microRNAs (
miRNAs) are important regulators of skeletal muscle size, and circulating
miRNAs within extracellular vesicles (EVs) may contribute to
atrophy and its associated systemic effects. The purpose of this study was to understand how
muscle atrophy and regrowth alter in vivo serum EV
miRNA content. We also associated changes in serum EV
miRNA with
protein synthesis, protein degradation, and
miRNA within muscle, kidney, and liver. We subjected adult (10 mo) F344/BN rats to three conditions: weight bearing (WB), hindlimb suspension (HS) for 7 days to induce
muscle atrophy, and HS for 7 days followed by 7 days of reloading (HSR). Microarray analysis of EV
miRNA content showed that the overall changes in serum EV
miRNA were predicted to target major anabolic, catabolic, and mechanosensitive pathways. MiR-203a-3p was the only
miRNA demonstrating substantial differences in HS EVs compared with WB. There was a limited association of EV
miRNA content to the corresponding
miRNA content within the muscle, kidney, or liver. Stepwise linear regression demonstrated that EV miR-203a-3p was correlated with muscle mass and
muscle protein synthesis and degradation across all conditions. Finally, EV miR-203a-3p expression was significantly decreased in human subjects who underwent unilateral lower limb
suspension (ULLS) to induce
muscle atrophy. Altogether, we show that serum EV miR-203a-3p expression is related to skeletal muscle
protein turnover and
atrophy. We suggest that serum EV miR-203a-3p content may be a useful
biomarker and future work should investigate whether serum EV miR-203a-3p content is mechanistically linked to
protein synthesis and degradation.