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J Physiol Volume 582, Number 2, 825-841, July 15, 2007 DOI: 10.1113/jphysiol.2007.132373
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Right arrow Skeletal Muscle and Exercise

SKELETAL MUSCLE AND EXERCISE

Mechanisms of skeletal muscle injury and repair revealed by gene expression studies in mouse models

 Gordon L. Warren1, Mukesh Summan2, Xin Gao2, Rebecca Chapman2, Tracy Hulderman2 and Petia P. Simeonova2

1 Division of Physical Therapy, Georgia State University, Atlanta GA 30303, USA
2 Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

Common acute injuries to skeletal muscle can lead to significant pain and disability. The current therapeutic approaches for treating muscle injuries are dependent on the clinical severity but not on the type of injury. In the present studies, the pathophysiology and molecular pathways associated with two different types of skeletal muscle injury, one induced by direct destruction of muscle tissue (i.e. FI) and the other induced by a contractile overload (more specifically high-force eccentric contractions, i.e. CI) were compared side by side. Histopathological evaluation and measurements of muscle strength were accompanied by analyses of expression for 12 488 known genes at four time points ranging from 6 h to 7 days after injury. Real-time RT-PCR was used to confirm some of the injury type differences in the temporal profiles of gene expression. Our data revealed several pools of genes, including early induction of transcription, myogenic and stress-responsive factors, common for both types of injury as well as pools of genes expressed specifically with one of the injury types. Only CI activated a set of genes associated with the repair of impaired proteins and structures including genes related to apoptosis, whereas FI uniquely activated gene sets involved in extensive inflammatory responses, tissue remodelling, angiogenesis and myofibre/extracellular matrix synthesis. In conclusion, knowledge of the sets of genes associated specifically with the nature of the injury may have application for development of new strategies for acceleration of the recovery process in injured skeletal muscle.

(Received 14 March 2007; accepted after revision 2 May 2007; first published online 3 May 2007)
Corresponding author: P. P. Simeonova: National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA. Email: psimeonova{at}cdc.gov

This paper has online supplemental material.






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