Effects of spaceflight on murine skeletal muscle gene expression.
Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts toward faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations, we used both microarray expression analysis and real-time polymerase chain reaction to quantify shifts in mRNA levels in the gastrocnemius from mice flown on the 11-day, 19-h STS-108 shuttle flight and from normal gravity controls. Spaceflight data also were compared with the ground-based unloading model of hindlimb suspension, with one group of pure suspension and one of suspension followed by 3.5 h of reloading to mimic the time between landing and euthanization of the spaceflight mice. Analysis of microarray data revealed that 272 mRNAs were significantly altered by spaceflight, the majority of which displayed similar responses to hindlimb suspension, whereas reloading tended to counteract these responses. Several mRNAs altered by spaceflight were associated with muscle growth, including the phosphatidylinositol 3-kinase regulatory subunit p85alpha, insulin response substrate-1, the forkhead box O1 transcription factor, and MAFbx/atrogin1. Moreover, myostatin mRNA expression tended to increase, whereas mRNA levels of the myostatin inhibitor FSTL3 tended to decrease, in response to spaceflight. In addition, mRNA levels of the slow oxidative fiber-associated transcriptional coactivator peroxisome proliferator-associated receptor (PPAR)-gamma coactivator-1alpha and the transcription factor PPAR-alpha were significantly decreased in spaceflight gastrocnemius. Finally, spaceflight resulted in a significant decrease in levels of the microRNA miR-206. Together these data demonstrate that spaceflight induces significant changes in mRNA expression of genes associated with muscle growth and fiber type.
Allen
David L
DL
Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA.
Bandstra
Eric R
ER
Harrison
Brooke C
BC
Thorng
Seiha
S
Stodieck
Louis S
LS
Kostenuik
Paul J
PJ
Morony
Sean
S
Lacey
David L
DL
Hammond
Timothy G
TG
Leinwand
Leslie L
LL
Argraves
W Scott
WS
Bateman
Ted A
TA
Barth
Jeremy L
JL
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D019417:Hindlimb Suspension; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics* / Q000503:physiopathology; D055435:Myostatin / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D013026:Space Flight; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D014893:Weightlessness
D035683:MicroRNAs; D055435:Myostatin; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; C525912:Mstn protein, mouse; C546843:mTOR protein, mouse