Sphingosine-1-phosphate receptor 3 influences cell cycle progression in muscle satellite cells.
Sphingosine-1-phosphate receptor 3 influences cell cycle progression in muscle satellite cells.
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DOI：
10.1016/j.ydbio.2013.07.006
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发表时间：
2013-10-15
影响因子：
2.7
通讯作者：
Zammit, Peter S.
中科院分区：
文献类型：
--
作者：
Fortier, Mathieu;Figeac, Nicolas;White, Robert B.;Knopp, Paul;Zammit, Peter S.
关键词：
骨骼肌保留了称为卫星细胞的常驻干细胞群，其在成熟肌肉中处于有丝分裂静止状态，但可以被激活以产生成肌细胞后代用于肌肉稳态、肥大和修复。我们以前已经表明，卫星细胞的激活是部分控制的生物活性磷脂，鞘氨醇-1-磷酸，和S1P的生物合成是肌肉再生所需的。在这里，我们研究鞘氨醇-1-磷酸受体3（S1PR3）在调节小鼠卫星细胞功能的作用。S1PR3水平在静止的肌源性细胞中较高，然后在进入细胞周期期间下降。逆转录病毒介导的S1PR3组成型表达导致卫星细胞的细胞周期进程受到抑制，但并没有明显影响肌原性程序。相反，从S1PR3缺失小鼠分离的卫星细胞表现出增强的离体增殖。在体内，急性心脏毒素诱导的肌肉再生在S1PR3缺失小鼠中得到增强，与对照小鼠相比具有更大的肌肉纤维。重要的是，在Duchenne肌营养不良症mdx小鼠模型中基因缺失S1PR3产生了不太严重的肌肉营养不良表型，而不是当通过S1PR3进行信号传导时。总之，信号通过S1PR3抑制细胞周期进程，以调节肌肉卫星细胞的功能。S1PR3的表达与非周期性成肌细胞相关。S1PR3的组成型表达导致细胞增殖减少。缺乏S1PR3的卫星细胞具有增强的增殖。肌肉再生在缺乏S1PR3的情况下得到改善。mdx小鼠中的营养不良表型通过缺乏S1PR3而改善。
Skeletal muscle retains a resident stem cell population called satellite cells, which are mitotically quiescent in mature muscle, but can be activated to produce myoblast progeny for muscle homeostasis, hypertrophy and repair. We have previously shown that satellite cell activation is partially controlled by the bioactive phospholipid, sphingosine-1-phosphate, and that S1P biosynthesis is required for muscle regeneration. Here we investigate the role of sphingosine-1-phosphate receptor 3 (S1PR3) in regulating murine satellite cell function. S1PR3 levels were high in quiescent myogenic cells before falling during entry into cell cycle. Retrovirally-mediated constitutive expression of S1PR3 led to suppressed cell cycle progression in satellite cells, but did not overtly affect the myogenic program. Conversely, satellite cells isolated from S1PR3-null mice exhibited enhanced proliferation ex-vivo. In vivo, acute cardiotoxin-induced muscle regeneration was enhanced in S1PR3-null mice, with bigger muscle fibres compared to control mice. Importantly, genetically deleting S1PR3 in the mdx mouse model of Duchenne muscular dystrophy produced a less severe muscle dystrophic phenotype, than when signalling though S1PR3 was operational. In conclusion, signalling though S1PR3 suppresses cell cycle progression to regulate function in muscle satellite cells. Expression of S1PR3 is associated with non-cycling myoblasts. Constitutive expression of S1PR3 leads to reduced cell proliferation. Satellite cells lacking S1PR3 have enhanced proliferation. Muscle regeneration is improved in the absence of S1PR3. The dystrophic phenotype in mdx mice is improved by the absence of S1PR3.
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影响因子：
5.2
作者：
Hsu A;Zhang W;Lee JF;An J;Ekambaram P;Liu J;Honn KV;Klinge CM;Lee MJ
通讯作者：
Lee MJ
影响因子：
3.3
作者：
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影响因子：
11.8
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通讯作者：
Hla, Timothy
影响因子：
4.8
作者：
Donati, C;Meacci, E;Bruni, P
通讯作者：
Bruni, P
影响因子：
4
作者：
Formigli, Lucia;Sassoli, Chiara;Meacci, Elisabetta
通讯作者：
Meacci, Elisabetta