α7β1 integrin regulation of skeletal muscle growth in response to mechanical loading

The α7β1 integrin has been proposed to serve as a mechanosensor and essential regulator of myofiber remodeling given its localization at the membrane and primary role in adhering the outer extracellular matrix to the inner actin cytoskeleton. However, additional work is necessary to affirm a primary role for the α7β1 integrin subunit in the regulation of skeletal muscle mass in response to mechanical loading. The purpose of this study was to 1) to utilize an automated computer program (SMASH) to reassess myofiber cross-sectional area in previously collected samples, and 2) to determine the mechanism by which the α7β1 integrin can promote myofiber growth following a mechanical stimulus. Aim 1 used an automated computer program to re- analyze myofiber CSA and confirm a role for the α7β1 integrin in myofiber hypertrophy following chronic mechanical loading. Aim 2 assessed potential mechanisms for integrin-mediated growth in response to chronic mechanical load, including upregulation of Yes-associated protein (YAP) content in skeletal muscle. The results from this study suggest that 1) the use of an automated computed program (SMASH) provides results that are comparable to manual measurement, 2) chronic mechanical loading elicits an increase in fiber splitting that may result in an underestimation of myofiber CSA, and 3) overexpression of the α7 integrin subunit increases baseline YAP content in skeletal muscle, an event that may influence the rate of myofiber hypertrophy in response to load. Future studies will incorporate the SMASH program for assessment of myofiber size while continuing to probe the mechanistic basis for integrin-mediated myofiber growth in response to load