Roles of IL-1α/β in regeneration of cardiotoxin-injured muscle and satellite cell function
Roles of IL-1α/β in regeneration of cardiotoxin-injured muscle and satellite cell function
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DOI：
10.1152/ajpregu.00310.2017
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发表时间：
2018-07-01
影响因子：
2.8
通讯作者：
Kanzaki, Makoto
中科院分区：
文献类型：
--
作者：
Chaweewannakorn, Chayanit;Tsuchiya, Masahiro;Kanzaki, Makoto
骨骼肌损伤后的再生是一个复杂的过程，涉及炎性微环境和卫星细胞之间的相互作用。白细胞介素2(IL)-L是炎症反应的关键介质，对多种细胞类型具有多效性影响。因此，我们旨在研究IL-J在骨骼肌再生中的作用。我们在此发现，与野生型(WT)小鼠相比，IL-1a/fidoublc基因敲除(1L-1KO)小鼠在注射心脏毒素(CTX)后表现出肌肉再生延迟，特征是免疫细胞渗透延迟，并伴有包括IL-6在内的局部炎性因子的抑制，以及配对盒7(PAX7)阳性卫星细胞的延迟增加。一系列使用从IL-1KO小鼠获得的卫星细胞的体外实验意外地发现，IL-1KO成肌细胞在增殖和分化方面都有损伤，这两种损伤都可以被培养中的外源性IL-1FI逆转。有趣的是，肌肉发生的延迟并不是由于肌肉生成的转录程序，因为在IL-1 KO细胞中MyoD和肌肉生成素高度上调，相反，似乎至少部分是由于细胞融合事件的失调，可能是由异常的肌动蛋白调控系统引起的。我们认为，IL-1通过协调炎症微环境和卫星细胞之间的初始相互作用，在肌肉再生中起着积极的作用。我们的发现也提供了令人信服的证据，表明IL-1密切参与调节心肌细胞的基本功能。
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.