Exercise promotes α7 integrin gene transcription and protection of skeletal muscle

The alpha 7 beta 1 integrin is increased in skeletal muscle in response to injury-producing exercise, and transgenic overexpression of this integrin in mice protects against exercise-induced muscle damage. The present study investigates whether the increase in the alpha 7 beta 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 alpha 7 integrin gene in 5-wk-oldwild-type mice 3 h postexercise, and an increased alpha 7A chain was detected in muscle sarcolemma adjacent to tendinous tissue immediately following exercise. The alpha 7B, but not alpha 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 alpha 7(-/-) mice. Muscle damage was extensive in alpha 7(-/-) 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 alpha 7 integrin gene and promotes a rapid change in the alpha 7 beta integrin at the MTJ. These combined molecular and cellular alterations are likely responsible for integrin-mediated attenuation of exercise-induced muscle damage.