Serum extracellular vesicle miR-203a-3p content is associated with skeletal muscle mass and protein turnover during disuse atrophy and regrowth

Douglas W. Van Pelt, Ivan J. Vechetti, Marcus M. Lawrence, Kathryn L. Van Pelt, Parth Patel, Benjamin F. Miller, Timothy A. Butterfield, Esther E. Dupont-Versteegden

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Serum extracellular vesicle miR-203a-3p content is associated with skeletal muscle mass and protein turnover during disuse atrophy and regrowth. Am J Physiol Cell Physiol 319: C419-C431, 2020. First published July 8, 2020; doi:10.1152/ajpcell.00223.2020. - 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.

Original languageEnglish
Pages (from-to)C419-C431
JournalAmerican Journal of Physiology - Cell Physiology
Volume319
Issue number2
DOIs
StatePublished - Aug 2020

Bibliographical note

Funding Information:
This work was supported by NIH Grant AT-009268 (E.E.D.-V, T.A.B., and B.F.M.). The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. The content is solely the responsibility if the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
Copyright © 2020 the American Physiological Society.

Keywords

  • Atrophy
  • Extracellular vesicles
  • MiRNA
  • Protein synthesis
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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