Repair of damaged muscle tissue upon acute injury requires the coordinated action of infiltrating inflammatory cells and activated muscle stem cells known as satellite cells to restore homeostasis. S100B protein regulates myoblast proliferation and differentiation, and its effects depend on its concentration, the myoblast density, the presence of bFGF, and the duration of exposure of myoblasts to the protein (1,2). S100B is abundantly released during the first few days after acute muscle injury and its release rapidly declines thereafter (2). The role of myofiber-released S100B is not known. Here we report that following injury with BaCl2 injection myofiber-released S100B expands the myoblast population, attracts macrophages to the site of damage, and promotes macrophage polarization into M2 (pro-regenerative) phenotype. Also, S100B is transiently expressed in and released by macrophages in response to cytokines. S100B effects are mediated by RAGE (receptor for advanced glycation end-products) in the early phase of muscle regeneration, however during the myoblast proliferation phase S100B also activates the bFGF-FGFR1 complex to stimulate myoblast proliferation and macrophage M1/M2 transition. Thus, S100B controls macrophage phenotypic transition and myoblast activity following acute muscle damage. Our data point to S100B as to a physiological player required for correct timing of skeletal muscle regeneration. However, high amounts of S100B at damage sites early after injury are detrimental causing prolongation of the myoblast proliferation phase at the expense of myoblast differentiation/fusion, larger infiltration with M1 macrophages, prolongation of the macrophage M1 phase, and deposition of fibrotic tissue. Thus, if present in high amounts S100B might contribute to the pathophysiology of muscle degenerative diseases characterized by chronic inflammation and/or deregulated muscle regeneration. 1. Riuzzi F. et al., J. Cell Sci 2011;124:2389-400. 2. Riuzzi F. et al., PLoS ONE 2012; 7: e28700.
S100B protein in skeletal muscle regeneration: regulation of myoblast and macrophage functions
RIUZZI, Francesca;BECCAFICO, SARA;SORCI, Guglielmo;DONATO, Rosario Francesco
2016
Abstract
Repair of damaged muscle tissue upon acute injury requires the coordinated action of infiltrating inflammatory cells and activated muscle stem cells known as satellite cells to restore homeostasis. S100B protein regulates myoblast proliferation and differentiation, and its effects depend on its concentration, the myoblast density, the presence of bFGF, and the duration of exposure of myoblasts to the protein (1,2). S100B is abundantly released during the first few days after acute muscle injury and its release rapidly declines thereafter (2). The role of myofiber-released S100B is not known. Here we report that following injury with BaCl2 injection myofiber-released S100B expands the myoblast population, attracts macrophages to the site of damage, and promotes macrophage polarization into M2 (pro-regenerative) phenotype. Also, S100B is transiently expressed in and released by macrophages in response to cytokines. S100B effects are mediated by RAGE (receptor for advanced glycation end-products) in the early phase of muscle regeneration, however during the myoblast proliferation phase S100B also activates the bFGF-FGFR1 complex to stimulate myoblast proliferation and macrophage M1/M2 transition. Thus, S100B controls macrophage phenotypic transition and myoblast activity following acute muscle damage. Our data point to S100B as to a physiological player required for correct timing of skeletal muscle regeneration. However, high amounts of S100B at damage sites early after injury are detrimental causing prolongation of the myoblast proliferation phase at the expense of myoblast differentiation/fusion, larger infiltration with M1 macrophages, prolongation of the macrophage M1 phase, and deposition of fibrotic tissue. Thus, if present in high amounts S100B might contribute to the pathophysiology of muscle degenerative diseases characterized by chronic inflammation and/or deregulated muscle regeneration. 1. Riuzzi F. et al., J. Cell Sci 2011;124:2389-400. 2. Riuzzi F. et al., PLoS ONE 2012; 7: e28700.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
