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.

Effects of aging, exercise, and disease on force transfer in skeletal muscle

“…Furthermore, in wild-type mice, the downhill running protocol led to increased expression and localization of ␣7A and ␣7B at the myotendinous junction. Along with these findings in transgenic mice, the integrin complexes are also altered during muscle contraction, hypertrophy, and contraction-induced injury in wild-type mice (12,49,53,121). These observations provide evidence toward the role of ␣7␤1-integrins in lateral force transmission and attenuating the development of contraction-induced injury.…”

Exercise-Induced Muscle Damage: Is it detrimental or beneficial?

“…Integrins are transmembrane receptors that allow chemical and mechanical signals to be transmitted from the outside of the cell to the inside of the cell and could play a role in the muscle hypertrophic response 68 . Consistent with this idea, the mice that overexpressed α7-integrin significantly increased muscle hypertrophy after 4 weeks of downhill running 67 . On the other hand, wild-type mice without overexpression of α7-integrin that performed downhill running for 4 weeks did not significantly increase in muscle size.…”

“…However, little muscle hypertrophy may result from this type of training. Recently, Zou et al 67 investigated the influence of downhill training in wild type mice and mice with an overexpression of α7-integrin. Integrins are transmembrane receptors that allow chemical and mechanical signals to be transmitted from the outside of the cell to the inside of the cell and could play a role in the muscle hypertrophic response 68 .…”

The effects of high fat diet and moderate exercise on TGFβ1 and collagen deposition in mouse skeletal muscle

“…Muscle protein was processed as previously published [24]. Briefly, powdered muscle was homogenized in ice-cold buffer.…”