Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration

Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration
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DOI:
10.1152/ajpcell.00072.2009
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发表时间:
2010-03-01
影响因子:
5.5
通讯作者:
Betto, Romeo
Betto, Romeo
中科院分区:
生物学2区
文献类型:
--
作者:
Danieli-Betto, Daniela;Peron, Samantha;Betto, Romeo

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Danieli-Betto D、Peron S、Germinario E、Zanin M、Sorci G、Franzoso S、Sandona D、Betto R。 1-磷酸鞘氨醇信号传导参与骨骼肌再生。 Am J Physiol Cell Physiol 298:C550-C558,2010。首次发表于 2009 年 12 月 30 日; doi: 10.1152/ajpcell.00072.2009.-1-磷酸鞘氨醇 (S1P) 是一种生物活性脂质,已知可控制细胞生长,最近被证明可作为骨骼肌的营养因子,减少失神经萎缩的进展。这项工作的目的是调查 S1P 是否参与布比卡因引起的肌肉毒性损伤后骨骼肌纤维的恢复(再生)。骨骼肌的出生后生长和再生能力取决于称为卫星细胞的常驻干细胞。免疫荧光分析表明,S1P 特异性受体 S1P(1) 和 S1P(3) 由静止卫星细胞表达。肌内注射布比卡因引起损伤后进行再生的比​​目鱼肌表现出S1P(1)受体表达增强,而S1P(3)表达逐渐降低至成人水平。 S1P(2)受体在静止细胞中不存在,但仅在早期再生阶段短暂表达。在肌肉毒性损伤时施用S1P(50μM)导致大鼠和小鼠再生纤维的平均横截面积显着增加。在旨在测试 S1P 营养作用的单独实验中,通过腹膜内施用抗 S1P 抗体来中和内源性循环 S1P,从而减弱纤维生长。使用 S1P 受体选择性调节剂表明,S1P(1) 受体和 S1P(3) 受体对再生的早期阶段具有正向调节作用,而 S1P(2) 受体似乎不太重要。目前的结果表明,S1P 信号传导参与骨骼肌的再生过程。
Danieli-Betto D, Peron S, Germinario E, Zanin M, Sorci G, Franzoso S, Sandona D, Betto R. Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration. Am J Physiol Cell Physiol 298: C550-C558, 2010. First published December 30, 2009; doi: 10.1152/ajpcell.00072.2009.-Sphingosine 1-phosphate (S1P) is a bioactive lipid known to control cell growth that was recently shown to act as a trophic factor for skeletal muscle, reducing the progress of denervation atrophy. The aim of this work was to investigate whether S1P is involved in skeletal muscle fiber recovery (regeneration) after myotoxic injury induced by bupivacaine. The postnatal ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. Immunofluorescence analysis demonstrated that S1P-specific receptors S1P(1) and S1P(3) are expressed by quiescent satellite cells. Soleus muscles undergoing regeneration following injury induced by intramuscular injection of bupivacaine exhibited enhanced expression of S1P(1) receptor, while S1P(3) expression progressively decreased to adult levels. S1P(2) receptor was absent in quiescent cells but was transiently expressed in the early regenerating phases only. Administration of S1P (50 mu M) at the moment of myotoxic injury caused a significant increase of the mean cross-sectional area of regenerating fibers in both rat and mouse. In separate experiments designed to test the trophic effects of S1P, neutralization of endogenous circulating S1P by intraperitoneal administration of anti-S1P antibody attenuated fiber growth. Use of selective modulators of S1P receptors indicated that S1P(1) receptor negatively and S1P(3) receptor positively modulate the early phases of regeneration, whereas S1P(2) receptor appears to be less important. The present results show that S1P signaling participates in the regenerative processes of skeletal muscle.