Abstract
Skeletal muscle has an ability to regenerate in response to injury due to the presence of satellite cells. Injury in skeletal muscle causes infiltration of pro-inflammatory macrophages (M1 macrophages) to remove necrotic myofibers, followed by their differentiation into anti-inflammatory macrophages (M2 macrophages) to terminate the inflammation. Since both M1 and M2 macrophages play important roles, coordinated regulation of their kinetics is important to complete muscle regeneration successfully. Progranulin (PGRN) is a pluripotent growth factor, having a protective role against the inflamed tissue. In the central nervous system, PGRN regulates inflammation by inhibiting the activation of microglia. Here we used muscle injury model of PGRN-knockout (PGRN-KO) mice to elucidate whether it has a role in the kinetics of macrophages during muscle regeneration. We found the prolonged persistence of macrophages at the late phase of regeneration in PGRN-KO mice, and these macrophages were suggested to be M2 macrophages since this was accompanied with an increased CD206 expression. We also observed muscle hypertrophy in PGRN-KO mice at the late stage of muscle regeneration. Since M2 macrophages are known to have a role in maturation of myofibers, this muscle hypertrophy may be due to the presence of increased number of M2 macrophages. Our results suggest that PGRN plays a role in the regulation of kinetics of macrophages for the systemic progress of muscle regeneration.