title: The α₇β₁-integrin increases muscle hypertrophy following multiple bouts of eccentric exercise.
abstract: Mechanical stimuli increase skeletal muscle growth in a mammalian target of rapamycin (mTOR)- and p70(S6K)-dependent manner. It has been proposed that costameric proteins at Z bands may sense and transfer tension to these initiators of protein translation, but few candidates have been identified. The purpose of this study was to determine whether a role exists for the α(7)-integrin in the activation of hypertrophic signaling and growth following eccentric exercise training. Five-week-old, wild-type (WT) and α(7)BX2-integrin transgenic (α(7)Tg) mice were randomly assigned to one of two groups: 1) sedentary (SED), or 2) exercise training (EX). Exercise training consisted of downhill running 3 sessions/wk for 4 wk (-20°, 17 m/min, 30 min). Downhill running was used to induce physiological mechanical strain. Twenty-four hours following the final training session, maximal isometric hindlimb plantar flexor force was measured. Gastrocnemius-soleus complexes were collected for further analysis of signaling changes, which included AKT, mTOR and p70(S6K), and muscle growth. Despite increased p70(S6K) activity in WT/EX, no significant changes in cross-sectional area or force were observed in WT/EX compared with WT/SED. AKT, mTOR, and p70(S6K) activation was higher, and whole muscle hypertrophy, relative muscle weight, myofibrillar protein, and force were significantly elevated in α(7)Tg/EX compared with α(7)Tg/SED. A marked increase in average myofiber cross-sectional area was observed in α(7)Tg/EX compared with all groups. Our findings demonstrate that the α(7)β(1)-integrin sensitizes skeletal muscle to mechanical strain and subsequent growth. Thus the α(7)β(1)-integrin may represent a novel molecular therapy for the treatment of disuse muscle atrophy.
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois, Urbana, Illinois, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Zou
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Meador
authors.forename: Brian
authors.initials: B
authors.lastname: Johnson
authors.forename: Heather D
authors.initials: HD
authors.lastname: Huntsman
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mahmassani
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Valero
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Huey
authors.forename: Marni D
authors.initials: MD
authors.lastname: Boppart
mesh_terms: D000818:Animals; D005260:Female; D006984:Hypertrophy; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009210:Myofibrils / Q000378:metabolism / Q000502:physiology; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012420:Running / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016023:Integrins; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C082908:integrin alpha7beta1