Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 315, Issue 1, Pages R90-R103Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00310.2017
Keywords
actin remodeling; fusion error; IL-1; IL-1-deficient mice; muscle regeneration; myoblasts; satellite cells
Categories
Funding
- Japan Society for the Promotion of Science [26670099, 24390429, 16K11580]
- Takeda Science Foundation
Ask authors/readers for more resources
Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite ceils. Interleukin (IL)-l is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-J during skeletal muscle regeneration. We herein show that IL-la/fidoublc knockout (1L-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)-posilive satellite cells postinjury compared with those of wild-type (WT) mice. A series of in vitro experiments using satellite cells obtained from the IL-1 KO mice unexpectedly revealed that IL-1KO myoblasts have impairments in terms of both proliferation and differentiation, both of which were reversed by exogenous IL-1 fi 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-1 KO 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available