TY - JOUR
T1 - Roles of il-1α/β in regeneration of cardiotoxin-injured muscle and satellite cell function
AU - Chaweewannakorn, Chayanit
AU - Tsuchiya, Masahiro
AU - Koide, Masashi
AU - Hatakeyama, Hiroyasu
AU - Tanaka, Yukinori
AU - Yoshida, Shinichirou
AU - Sugawara, Shunji
AU - Hagiwara, Yoshihiro
AU - Sasaki, Keiichi
AU - Kanzaki, Makoto
N1 - Funding Information:
This work was supported in part by grants from the Japan Society for the Promotion of Science (no. 26670099 to M. Kanzaki and nos. 24390429 and 16K11580 to M. Tsuchiya) and the Takeda Science Foundation (to M. Kanzaki).
Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.
PY - 2018/7/2
Y1 - 2018/7/2
N2 - Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite cells. Interleukin (IL)-1 is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-1 during skeletal muscle regeneration. We herein show that IL-1α/β-double knockout (IL-1KO) mice exhibit delayed muscle regeneration after cardiotoxin (CTX) injection, characterized by delayed infiltrations of immune cells accompanied by suppressed local production of proinflammatory factors including IL-6 and delayed increase of paired box 7 (PAX7)-positive satellite cells postinjury compared with those of wild-type (WT) mice. A series of in vitro experiments using satellite cells obtained from the IL-1KO mice unexpectedly revealed that IL-1KO myoblasts have impairments in terms of both proliferation and differentiation, both of which were reversed by exogenous IL-1β administration in culture. Intriguingly, the delay in myogenesis was not attributable to the myogenic transcriptional program since MyoD and myogenin were highly upregulated in IL-1KO cells, instead appearing, at least in part, to be due to dysregulation of cellular fusion events, possibly resulting from aberrant actin regulatory systems. We conclude that IL-1 plays a positive role in muscle regeneration by coordinating the initial interactions among inflammatory microenvironments and satellite cells. Our findings also provide compelling evidence that IL-1 is intimately engaged in regulating the fundamental function of myocytes.
AB - Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite cells. Interleukin (IL)-1 is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-1 during skeletal muscle regeneration. We herein show that IL-1α/β-double knockout (IL-1KO) mice exhibit delayed muscle regeneration after cardiotoxin (CTX) injection, characterized by delayed infiltrations of immune cells accompanied by suppressed local production of proinflammatory factors including IL-6 and delayed increase of paired box 7 (PAX7)-positive satellite cells postinjury compared with those of wild-type (WT) mice. A series of in vitro experiments using satellite cells obtained from the IL-1KO mice unexpectedly revealed that IL-1KO myoblasts have impairments in terms of both proliferation and differentiation, both of which were reversed by exogenous IL-1β administration in culture. Intriguingly, the delay in myogenesis was not attributable to the myogenic transcriptional program since MyoD and myogenin were highly upregulated in IL-1KO cells, instead appearing, at least in part, to be due to dysregulation of cellular fusion events, possibly resulting from aberrant actin regulatory systems. We conclude that IL-1 plays a positive role in muscle regeneration by coordinating the initial interactions among inflammatory microenvironments and satellite cells. Our findings also provide compelling evidence that IL-1 is intimately engaged in regulating the fundamental function of myocytes.
KW - Actin remodeling
KW - Fusion error
KW - Il-1
KW - Il-1-deficient mice
KW - Muscle regeneration
KW - Myoblasts
KW - Satellite cells
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U2 - 10.1152/ajpregu.00310.2017
DO - 10.1152/ajpregu.00310.2017
M3 - Article
C2 - 29513560
AN - SCOPUS:85047337731
VL - 315
SP - R90-R103,
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 1
ER -