RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth

Chiara Noviello; Kassandra Kobon; Léa Delivry; Thomas Guilbert; Florian Britto; Francis Julienne; Pascal Maire; Voahangy Randrianarison-Huetz; Athanassia Sotiropoulos

doi:10.1016/j.isci.2021.103616

RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth

iScience. 2021 Dec 11;25(1):103616. doi: 10.1016/j.isci.2021.103616. eCollection 2022 Jan 21.

Authors

Chiara Noviello^{1

2

3}, Kassandra Kobon^{1

2

3}, Léa Delivry^{1

2

3}, Thomas Guilbert^{1

2

3}, Florian Britto^{1

2

3}, Francis Julienne^{1

2

3}, Pascal Maire^{1

2

3}, Voahangy Randrianarison-Huetz^{1

2

3}, Athanassia Sotiropoulos^{1

2

3}

Affiliations

¹ Inserm U1016, Institut Cochin, F-75014 Paris, France.
² CNRS UMR8104, F-75014 Paris, France.
³ Université de Paris, F-75006 Paris, France.

Abstract

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 (SC) fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such as Mmp9/Mmp13/Adam8 and macrophage chemo-attractants such as Ccl3/Cx3cl1. Their decreased expression in RhoA mutants is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, matrix metalloproteinases inhibition and macrophage depletion in controls phenocopied the altered growth of RhoA mutants while having no effect in mutants showing that their action is RhoA-dependent. These findings unravel the implication of RhoA within myofibers, in the building of a permissive microenvironment for muscle hypertrophic growth and for SC accretion through ECM remodeling and inflammatory cell recruitment.

Keywords: Biological sciences; Cell biology; Functional aspects of cell biology; Stem cells research.