Purinoceptor expression in regenerating skeletal muscle in the mdx mouse model of muscular dystrophy and in satellite cell cultures

Purinoceptor expression in regenerating skeletal muscle in the mdx mouse model of muscular dystrophy and in satellite cell cultures
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肌营养不良症 mdx 小鼠模型和卫星细胞培养物再生骨骼肌中嘌呤受体的表达

DOI:
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发表时间:
2004
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
G. Burnstock
G. Burnstock
中科院分区:
--
文献类型:
--
作者:
M. Ryten;Shi;P. M. Dunn;G. Goldspink;G. Burnstock

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ATP是一种重要的细胞外信号分子,通过激活P2 X和P2 Y受体介导其作用。P2受体在肌肉发育过程中表达,最近的研究表明ATP可以调节成肌细胞的增殖和分化。然而,嘌呤能信号转导在损伤骨骼肌再生过程中的作用尚未研究。为了在临床相关系统中检查这一过程,我们使用了肌营养不良症(mdx)小鼠模型,其中肌肉变性迅速随后再生。后一个过程,在体内肌肉再生,是本研究的重点,并研究参与其中的细胞机制,正常大鼠骨骼肌成肌细胞培养的平行研究进行。使用免疫组织化学、RT-PCR和电生理学,我们研究了P2 X1 - 7受体亚型和P2 Y1、2、4、6受体的表达。体外和体内实验证实了在肌肉再生过程中P2 X5、P2 Y1和P2 X2受体的顺序表达。P2 X5和P2 Y1受体首先在活化的卫星细胞上表达,P2 Y1受体也在浸润的免疫细胞上表达。随后的P2 X2受体表达新形成的肌管表现出显着的共定位与乙酰胆碱受体,这表明在调节肌肉神经支配的作用。因此,这项研究提供了嘌呤能信号在肌肉再生中的作用的第一个证据,并提出了新的治疗策略在治疗肌肉疾病的可能性。
ATP is an important extracellular signaling molecule mediating its effects by activation of P2X and P2Y receptors. P2 receptors are expressed during muscle development, and recent findings demonstrate that ATP can regulate myoblast proliferation and differentiation in vitro. However, the role of purinergic signaling during regeneration of injured skeletal muscle has not been investigated. To examine this process in a clinically relevant system, we used the mouse model of muscular dystrophy (mdx), in which muscle degeneration is rapidly followed by regeneration. The latter process, in vivo muscle regeneration, was the focus of this study, and to study the cellular mechanisms involved in it, a parallel study on normal rat skeletal myoblast cultures was conducted. Using immunohistochemistry, RT‐PCR, and electrophysiology, we investigated the expression of the P2X1‐7 receptor subtypes and the P2Y1,2,4,6 receptors. Experiments in vitro and in vivo demonstrated the sequential expression of the P2X5, P2Y1, and P2X2 receptors during the process of muscle regeneration. The P2X5 and P2Y1 receptors were expressed first on activated satellite cells, and the P2Y1 receptor was also expressed on infiltrating immune cells. Subsequent P2X2 receptor expression on newly formed myotubes showed significant colocalization with AChRs, suggesting a role in regulation of muscle innervation. Thus, this study provides the first evidence for a role for purinergic signaling in muscle regeneration and raises the possibility of new therapeutic strategies in the treatment of muscle disease.
ATP 与乙酰胆碱一起释放,作为青蛙运动神经末梢神经肌肉抑制的介质。
DOI: 10.1113/jphysiol.1994.sp020176
发表时间: 1994
期刊: The Journal of physiology
影响因子: --
作者:
Redman,RS;Silinsky,EM
通讯作者: Silinsky,EM
青蛙运动神经冲动发生后几毫秒内同步释放 ATP 和神经递质。
DOI: 10.1113/jphysiol.1996.sp021348
发表时间: 1996
期刊: The Journal of physiology
影响因子: --
作者:
Silinsky,EM;Redman,RS
通讯作者: Redman,RS
大鼠神经肌肉传递过程中释放的腺苷来源。
DOI: 10.1113/jphysiol.1991.sp018388
发表时间: 1991
期刊: The Journal of physiology
影响因子: --
作者:
Smith,DO
通讯作者: Smith,DO
DOI: 10.1073/pnas.90.8.3710
发表时间: 1993-04-15
影响因子: 11.1
作者:
PETROF, BJ;SHRAGER, JB;SWEENEY, HL
通讯作者: SWEENEY, HL