The α7β1-integrin increases muscle hypertrophy following multiple bouts of eccentric exercise

Zou K, Meador BM, Johnson B, Huntsman HD, Mahmassani Z, Valero MC, Huey KA, Boppart MD. The alpha(7 beta 1)-integrin increases muscle hypertrophy following multiple bouts of eccentric exercise. J Appl Physiol 111: 1134-1141, 2011. First published August 4, 2011; doi:10.1152/japplphysiol.00081.2011.-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 alpha(7)-integrin in the activation of hypertrophic signaling and growth following eccentric exercise training. Five-week-old, wild-type (WT) and alpha(7)BX2-integrin transgenic (alpha(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 degrees, 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 alpha(7)Tg/EX compared with alpha(7)Tg/SED. A marked increase in average myofiber cross-sectional area was observed in alpha(7)Tg/EX compared with all groups. Our findings demonstrate that the alpha(7 beta 1)-integrin sensitizes skeletal muscle to mechanical strain and subsequent growth. Thus the alpha(7 beta 1)-integrin may represent a novel molecular therapy for the treatment of disuse muscle atrophy.