Extracellular microRNAs are dynamic non-vesicular biomarkers of muscle turnover.
Extracellular microRNAs (miRNAs) are promising biomarkers of the inherited muscle wasting condition Duchenne muscular dystrophy, as they allow non-invasive monitoring of either disease progression or response to therapy. In this study, serum miRNA profiling reveals a distinct extracellular miRNA signature in dystrophin-deficient mdx mice, which shows profound dose-responsive restoration following dystrophin rescue. Extracellular dystrophy-associated miRNAs (dystromiRs) show dynamic patterns of expression that mirror the progression of muscle pathology in mdx mice. Expression of the myogenic miRNA, miR-206 and the myogenic transcription factor myogenin in the tibialis anterior muscle were found to positively correlate with serum dystromiR levels, suggesting that extracellular miRNAs are indicators of the regenerative status of the musculature. Similarly, extracellular dystromiRs were elevated following experimentally-induced skeletal muscle injury and regeneration in non-dystrophic mice. Only a minority of serum dystromiRs were found in extracellular vesicles, whereas the majority were protected from serum nucleases by association with protein/lipoprotein complexes. In conclusion, extracellular miRNAs are dynamic indices of pathophysiological processes in skeletal muscle.
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA, Dubowitz Neuromuscular Centre, UCL Institute of Child Health, 30 Guildford Street, London, WC1N 1EH, UK and Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Thomas C
TC
Roberts
Caroline
C
Godfrey
Graham
G
McClorey
Pieter
P
Vader
Deborah
D
Briggs
Chris
C
Gardiner
Yoshitsugu
Y
Aoki
Ian
I
Sargent
Jennifer E
JE
Morgan
Matthew J A
MJ
Wood
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D035683:MicroRNAs / Q000097:blood*; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology* / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000097:blood* / Q000473:pathology / Q000628:therapy; D012038:Regeneration
D015415:Biomarkers; D001798:Blood Proteins; D035683:MicroRNAs