MicroRNA-155 facilitates skeletal muscle regeneration by balancing pro- and anti-inflammatory macrophages.
Skeletal muscle has remarkable regeneration capacity and regenerates in response to injury. Muscle regeneration largely relies on muscle stem cells called satellite cells. Satellite cells normally remain quiescent, but in response to injury or exercise they become activated and proliferate, migrate, differentiate, and fuse to form multinucleate myofibers. Interestingly, the inflammatory process following injury and the activation of the myogenic program are highly coordinated, with myeloid cells having a central role in modulating satellite cell activation and regeneration. Here, we show that genetic deletion of microRNA-155 (miR-155) in mice substantially delays muscle regeneration. Surprisingly, miR-155 does not appear to directly regulate the proliferation or differentiation of satellite cells. Instead, miR-155 is highly expressed in myeloid cells, is essential for appropriate activation of myeloid cells, and regulates the balance between pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages during skeletal muscle regeneration. Mechanistically, we found that miR-155 suppresses SOCS1, a negative regulator of the JAK-STAT signaling pathway, during the initial inflammatory response upon muscle injury. Our findings thus reveal a novel role of miR-155 in regulating initial immune responses during muscle regeneration and provide a novel miRNA target for improving muscle regeneration in degenerative muscle diseases.
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, 76 Linjiang Road, Chongqing, P.R. China.|Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, USA.
M
M
Nie
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, USA.
J
J
Liu
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, USA.|Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China.
Q
Q
Yang
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, USA.
H Y
HY
Seok
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, USA.
X
X
Hu
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, 76 Linjiang Road, Chongqing, P.R. China.
Z-L
ZL
Deng
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, USA.
D-Z
DZ
Wang
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D053612:Janus Kinases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032446:Myoblasts / Q000378:metabolism; D010641:Phenotype; D012038:Regeneration; D050791:STAT Transcription Factors / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism
D016207:Cytokines; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D050791:STAT Transcription Factors; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D053612:Janus Kinases