Boppart MD, Volker SE, Alexander N, Burkin DJ, Kaufman SJ. Exercise promotes ␣7 integrin gene transcription and protection of skeletal muscle. Am J Physiol Regul Integr Comp Physiol 295: R1623-R1630, 2008. First published September 10, 2008 doi:10.1152/ajpregu.00089.2008.-The ␣7␤1 integrin is increased in skeletal muscle in response to injury-producing exercise, and transgenic overexpression of this integrin in mice protects against exerciseinduced muscle damage. The present study investigates whether the increase in the ␣7␤1 integrin observed in wild-type mice in response to exercise is due to transcriptional regulation and examines whether mobilization of the integrin at the myotendinous junction (MTJ) is a key determinant in its protection against damage. A single bout of downhill running exercise selectively increased transcription of the ␣7 integrin gene in 5-wk-old wild-type mice 3 h postexercise, and an increased ␣7 chain was detected in muscle sarcolemma adjacent to tendinous tissue immediately following exercise. The ␣7B, but not ␣7A isoform, was found concentrated and colocalized with tenascin-C in muscle fibers lining the MTJ. To further validate the importance of the integrin in the protection against muscle damage following exercise, muscle injury was quantified in ␣7 Ϫ/Ϫ mice. Muscle damage was extensive in ␣7 Ϫ/Ϫ mice in response to both a single and repeated bouts of exercise and was largely restricted to areas of high MTJ concentration and high mechanical force near the Achilles tendon. These results suggest that exercise-induced muscle injury selectively increases transcription of the ␣7 integrin gene and promotes a rapid change in the ␣7␤ integrin at the MTJ. These combined molecular and cellular alterations are likely responsible for integrin-mediated attenuation of exercise-induced muscle damage. exercise; injury; repeated bout effect; tenascin-C SEVERAL CLASSES OF CELL ADHESION molecules provide mechanisms for attaching cells to each other and to their extracellular environment. These include integrins, cadherins, and members of the immunoglobulin and selectin families (23). Integrins are transmembrane heterodimers of noncovalently bound ␣-and ␤-subunits. Integrins bind to specific ligands in the extracellular matrix, form clusters, and recruit cytoskeletal and cytoplasmic proteins that stabilize the cell and provide a means for communication between the outside and inside of the cell. Eighteen ␣-subunits and 8 ␤-subunits have been characterized, and at least 24 heterodimers have been identified (46).␣7␤1 is the predominant integrin in adult skeletal muscle. The ␣7 subunit determines the specificity of ligand binding to laminin in the basal lamina surrounding individual muscle fibers, whereas the ␤1 subunit participates in linkage with actin via several subsarcolemmal proteins, including ␣-actinin, talin, vinculin, paxillin, and tensin. Several other integrin ␣-subunits are expressed in skeletal muscle in association with ␤1, including ␣1, ␣3, ␣4, ␣5, ␣6, ␣9, ␣10, ␣11, and ␣v (15,29,30,39,...

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