Exercise promotes alpha7 integrin gene transcription and protection of skeletal muscle.
The alpha7beta1 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 alpha7beta1 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 alpha7 integrin gene in 5-wk-old wild-type mice 3 h postexercise, and an increased alpha7 chain was detected in muscle sarcolemma adjacent to tendinous tissue immediately following exercise. The alpha7B, but not alpha7A 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 alpha7(-/-) mice. Muscle damage was extensive in alpha7(-/-) 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 alpha7 integrin gene and promotes a rapid change in the alpha7beta integrin at the MTJ. These combined molecular and cellular alterations are likely responsible for integrin-mediated attenuation of exercise-induced muscle damage.
Boppart
Marni D
MD
Department of Kinesiology and Community Health, University of Illinois, Urbana, Illinois, USA.
Volker
Sonja E
SE
Alexander
Nicole
N
Burkin
Dean J
DJ
Kaufman
Stephen J
SJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000502:physiology; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012420:Running / Q000502:physiology; D019063:Tenascin / Q000502:physiology; D013710:Tendons / Q000502:physiology
D015703:Antigens, CD; D018076:DNA, Complementary; D039001:Integrin alpha Chains; D019063:Tenascin; C085725:integrin alpha7; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
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