Key result
Myofiber RhoA deletion impairs overload-induced skeletal muscle hypertrophy by ~50% vs controls.
Absolute Event Rate: 15% vs 30%
RhoA within myofibers is essential for overload-induced skeletal muscle hypertrophy by regulating extracellular matrix remodeling and macrophage recruitment to facilitate satellite cell fusion.
RhoA required for overload hypertrophy in mice; leaves open relevance to human muscle adaptation or therapy.
Summary Adult skeletal muscle is a plastic tissue that can adapt its size to workload. Here, we show that RhoA within myofibers is needed for overload-induced hypertrophy by controlling satellite cell fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that, in response to increased workload, RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such as Mmp9/Mmp13/Adam8 and of macrophage chemo-attractants such as Ccl3 / Cx3cl1. Their decreased expression in RhoA mutant is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, Mmps inhibition and macrophage depletion in controls phenocopied the lack of growth of RhoA mutants. These findings unravel the implication of RhoA within myofibers, in response to increase load, in the building of a permissive microenvironment for muscle growth and for satellite cell accretion through ECM remodeling and inflammatory cell recruitment.
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Noviello et al. (2021) studied Skeletal muscle hypertrophy. RhoA deletion in myofibers vs. Control mice (RhoA expressing) was evaluated on Muscle weight increase after overload-induced hypertrophy. Deletion of RhoA within myofibers impaired overload-induced skeletal muscle hypertrophy, resulting in a 15% increase in muscle weight compared to a 30% increase in controls.
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