S1P2 receptor promotes mouse skeletal muscle regeneration

S1P2 receptor promotes mouse skeletal muscle regeneration
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DOI:
10.1152/japplphysiol.00300.2012
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发表时间:
2012-09-01
影响因子:
3.3
通讯作者:
Danieli-Betto, Daniela
Danieli-Betto, Daniela
中科院分区:
医学2区
文献类型:
--
作者:
Germinario, Elena;Peron, Samantha;Danieli-Betto, Daniela

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gerario E, Peron S, Toniolo L, Betto R, Cencetti F, Donati C, Bruni P, Danieli-Betto D. S1P(2)受体促进小鼠骨骼肌再生。中国生物医学工程学报(英文版),2012(3):444 - 444。首次发表于2012年6月28日;doi: 10.1152 / japplphysiol.00300.2012。-鞘氨醇1-磷酸是一种生物活性脂质,通过与定位于肌纤维和卫星细胞细胞膜上的特异性受体相互作用来调节骨骼肌的生长。本研究分析了两种S1P(2)缺乏模型中S1P(2)缺失小鼠和S1P(2)受体拮抗剂JTE-013治疗的野生型小鼠,S1P(2)受体在体内比目鱼肌再生中的作用。为了刺激再生,在比目鱼肌内注射肌毒性药物诺特辛诱导肌肉变性。S1P(2)受体的消融及其功能失活均延迟了比目鱼肌的再生。当S1P(2)受体缺失或失活时,外源性补充S1P或通过特定抗体去除S1P,这两种已知的分别刺激或抑制比目鱼肌再生的情况没有影响。再生延迟与肌生成素(肌肉分化标志物)水平降低和Akt(肌肉生长的关键标志物)磷酸化降低有关。与此一致的是,S1P(2)受体的沉默消除了卫星细胞中S1P的促肌作用,与低水平的肌原性转录因子myogenin相对应。该研究表明,S1P(2)受体通过维持新形成的肌纤维的分化和生长,在肌肉再生的早期阶段发挥关键作用。
Germinario E, Peron S, Toniolo L, Betto R, Cencetti F, Donati C, Bruni P, Danieli-Betto D. S1P(2) receptor promotes mouse skeletal muscle regeneration. J Appl Physiol 113: 707-713, 2012. First published June 28, 2012; doi: 10.1152/japplphysiol.00300.2012.-Sphingosine 1-phosphate is a bioactive lipid that modulates skeletal muscle growth through its interaction with specific receptors localized in the cell membrane of muscle fibers and satellite cells. This study analyzes the role of S1P(2) receptor during in vivo regeneration of soleus muscle in two models of S1P(2) deficiency: the S1P(2)-null mouse and wild-type mice systemically treated with the S1P(2) receptor antagonist JTE-013. To stimulate regeneration, muscle degeneration was induced by injecting into soleus muscle the myotoxic drug notexin. Both ablation of S1P(2) receptor and its functional inactivation delayed regeneration of soleus muscle. The exogenous supplementation of S1P or its removal, by a specific antibody, two conditions known to stimulate or inhibit, respectively, soleus muscle regeneration, were without effects when the S1P(2) receptor was absent or inactive. The delayed regeneration was associated with a lower level of myogenin, a muscle differentiation marker, and reduced phosphorylation of Akt, a key marker of muscle growth. Consistently, silencing of S1P(2) receptor abrogated the pro-myogenic action of S1P in satellite cells, paralleled by low levels of the myogenic transcription factor myogenin. The study indicates that S1P(2) receptor plays a key role in the early phases of muscle regeneration by sustaining differentiation and growth of new-forming myofibers.