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1 Division of Biology, 147-75, California Institute of Technology, Pasadena, CA, USA
2 Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
3 Department of Medicine, Duke University Medical Center, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: zhen.yan{at}duke.edu.
Skeletal muscle undergoes adaptation following repetitive bouts of exercise. We hypothesize that transcriptional reprogramming and cellular remodeling start in the early phase of long-term training and play an important role in skeletal muscle adaptation. The aim of this study was to
define the global mRNA expression in mouse plantaris muscle during (run for 3 and 12 hours) and after (3, 6, 12 and 24 hours post-exercise) a single bout of voluntary running and compare with that after long-term training (4 weeks of running). Among 15,832 gene elements surveyed
in a high-density cDNA microarray analysis, 900 showed more than 2-fold changes at one or more time points. K-means clustering and cumulative hypergeometric probability distribution analyses revealed a significant enrichment of genes involved in defense, cell cycle, cell adhesion
and motility, signal transduction and apoptosis with induced expression patterns sharing similar patterns with that of peroxisome proliferators activator receptor
co-activator 1
(Ppargc1a/Pgc-1
) and vascular endothelial growth factor A (Vegfa). We focused on the finding of a delayed (at 24 hours post-exercise) induction of mRNA expression of cell cycle genes, origin recognition complex 1, cyclin A2 and cell division 2 homolog A (S. pombe) and
confirmed increased cell proliferation by in vivo 5-bromo-2-deoxyuridine (BrdU) labeling following voluntary running. X-ray irradiation of the hindlimb significantly diminished exerciseinduced BrdU incorporation. These findings suggest that a single bout of voluntary running
activates the transcriptional network and promotes adaptive processes in skeletal muscle including cell proliferation.
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