The α7B1 Integrin Promotes Skeletal Muscle Hypertrophy Following Eccentric Exercise

Abstract

Myogenesis and/or new and preexisting fiber hypertrophy are primary factors responsible for muscle growth observed following eccentric exercise training. We have recently demonstrated that muscle-specific transgenic expression of the α7 integrin enhances de novo fiber synthesis in skeletal muscle following a single bout of eccentric exercise. PURPOSE: The purpose of this study was to determine the extent to which transgenic expression of the α7 integrin increases muscle fiber size and force generation following multiple bouts of eccentric exercise. METHODS: 5 wk old, female wild type (WT) (n=10) and α7BX2 integrin transgenic (α7Tg) (n=10) mice were randomly assigned to one of two groups: 1) sedentary (SED) or 2) exercise training (EX). Exercise training consisted of downhill running 3 times/wk for 4 wk (-20°, 17 m/min, 30 min). Twenty-four hr following the final training session, maximal isometric hindlimb plantarflexor force was measured via in situ stimulation of the sciatic nerve. Gastrocnemius-soleus complexes were collected for further analysis of fiber cross sectional areas (CSA). Analysis of signaling events reflective of protein synthesis (AKT and p70S6K) were completed on the contralateral limb. RESULTS: Whereas p70S6K phosphorylation was elevated 1.5-fold (P<0.05), no significant increases in average CSA (WT SED: 617.02 56.34 vs. WT EX: 847.77 76.18 mm2; NS), or hindlimb force were observed in the WT EX group compared to WT SED. In contrast, all AKT, mTOR and p70S6K phosphorylation were significantly elevated (AKT: 70%, mTOR: 2.0-fold; p70S6K: 1.3-fold; P<0.05) and concomitant increases in average CSA (α7Tg SED: 1280.80 62.25 mm2 vs. α7Tg EX: 1790.25 126.88; P<0.05) and hindlimb force (25.3%; P=0.054) were observed in the α7Tg EX group compared to α7Tg SED. The percentage of fibers ranging 2000 to 3000 mm2 increased 2.6-fold in α7Tg EX compared to α7Tg SED (P<0.05). CONCLUSION: The results from this study and our previous work demonstrate that the presence of the α7 integrin markedly enhances individual muscle fiber growth and suggest the α7B1 integrin is an important regulator of exercise-induced hypertrophy. Supported by grants from the Illinois Regenerative Medicine Institute, UIUC Arnold O. Beckman Award, and the Ellison Medical Foundation.