Myostatin negatively regulates satellite cell activation and self-renewal.
Myostatin negatively regulates satellite cell activation and self-renewal.
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DOI：
10.1083/jcb.200207056
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发表时间：
2003-09-15
影响因子：
7.8
通讯作者：
Kambadur, Ravi
中科院分区：
文献类型：
--
作者：
McCroskery, Seumas;Thomas, Mark;Maxwell, Linda;Sharma, Mridula;Kambadur, Ravi
卫星细胞是促进出生后肌肉生长和修复的静止肌肉干细胞。在这里，我们表明，肌生长抑制素，TGF-β成员，信号卫星细胞静止，也负调控卫星细胞自我更新。体内BrdU标记显示，在肌生长抑制素缺陷型卫星细胞中，与野生型相比，更多数量的卫星细胞被激活。相比之下，肌生长抑制素的肌纤维外植体培养物抑制卫星细胞活化。细胞周期分析证实，Myostatin上调了Cdk抑制剂p21，并降低了卫星细胞中Cdk 2蛋白的水平和活性。因此，肌生长抑制素负调控G1到S的进程，从而维持卫星细胞的静止状态。用CD 34抗体进行的免疫组织化学分析表明，新鲜分离的肌纤维每单位长度的卫星细胞数量增加。对增殖率的测定表明，卫星细胞数量的增加可能是由于MIBI −/−成体成肌细胞中的自我更新增加和分化基因（肌细胞生成素）的延迟表达。总之，这些结果表明，肌生长抑制素是卫星细胞激活的有效负调节剂，因此发出卫星细胞静止的信号。
Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-β member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures inhibits satellite cell activation. Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells. Hence, Myostatin negatively regulates the G1 to S progression and thus maintains the quiescent status of satellite cells. Immunohistochemical analysis with CD34 antibodies indicates that there is an increased number of satellite cells per unit length of freshly isolated Mstn−/− muscle fibers. Determination of proliferation rate suggests that this elevation in satellite cell number could be due to increased self-renewal and delayed expression of the differentiation gene (myogenin) in Mstn−/− adult myoblasts. Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.