Progranulin deficiency leads to prolonged persistence of macrophages,accompanied with myofiber hypertrophy in regenerating muscle

The Journal of Veterinary Medical Science

Takashi MATSUWAKI¹  Hidetoshi SUGIHARA¹  Keitaro YAMANOUCHI¹  Masugi NISHIHARA¹  Kei MIYAJI¹ 

[1] Department of Veterinary Physiology, Graduate School ofAgricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo113-8657, Japan

关键词: inflammation;    macrophage;    progranulin;    regeneration;    skeletal muscle;   

DOI  :  10.1292/jvms.17-0638

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

Skeletal muscle has an ability to regenerate in response to injury due to the presence ofsatellite cells. Injury in skeletal muscle causes infiltration of pro-inflammatorymacrophages (M1 macrophages) to remove necrotic myofibers, followed by theirdifferentiation into anti-inflammatory macrophages (M2 macrophages) to terminate theinflammation. Since both M1 and M2 macrophages play important roles, coordinatedregulation of their kinetics is important to complete muscle regeneration successfully.Progranulin (PGRN) is a pluripotent growth factor, having a protective role against theinflamed tissue. In the central nervous system, PGRN regulates inflammation by inhibitingthe 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 muscleregeneration. We found the prolonged persistence of macrophages at the late phase ofregeneration in PGRN-KO mice, and these macrophages were suggested to be M2 macrophagessince this was accompanied with an increased CD206 expression. We also observed musclehypertrophy in PGRN-KO mice at the late stage of muscle regeneration. Since M2 macrophagesare known to have a role in maturation of myofibers, this muscle hypertrophy may be due tothe presence of increased number of M2 macrophages. Our results suggest that PGRN plays arole in the regulation of kinetics of macrophages for the systemic progress of muscleregeneration.

【 授权许可】

Unknown