Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition
Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition
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DOI：
10.1002/1873-3468.13227
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发表时间：
2018-09-01
期刊：
影响因子：
3.5
通讯作者：
Dux, Laszlo
中科院分区：
文献类型：
--
作者：
Keller-Pinter, Aniko;Szabo, Kitti;Dux, Laszlo
肌生长抑制素是tgf - β超家族成员，是肌肉生长的负调节因子。在这里，我们描述了肌生长抑制素活性是如何被syndecan-4调节的，syndecan-4是一种普遍存在的跨膜硫酸肝素蛋白多糖。在肌肉再生过程中，syndecan-4和promyostatin的水平在急剧上升后逐渐下降，同时释放成熟的肌肉生长抑制素。促肌肉生长抑制素和syndecan-4共同免疫沉淀，相互作用对肝素酶敏感。shrna介导的syndecan-4的沉默通过阻断细胞周期从G1期到s期的进展来降低C2C12成肌细胞的增殖，这伴随着肌肉生长抑制素和p21（Waf1/Cip1）水平的升高，以及cyclin E和cyclin D1表达的降低。我们的研究结果表明syndecan-4作为肌生长抑制素的储存库，调节成熟肌生长抑制素的局部生物利用度。
Myostatin, a TGF-beta superfamily member, is a negative regulator of muscle growth. Here we describe how myostatin activity is regulated by syndecan-4, a ubiquitous transmembrane heparan sulfate proteoglycan. During muscle regeneration the levels of both syndecan-4 and promyostatin decline gradually after a sharp increase, concurrently with the release of mature myostatin. Promyostatin and syndecan-4 co-immunoprecipitate, and the interaction is heparinase-sensitive. ShRNA-mediated silencing of syndecan-4 reduces C2C12 myoblast proliferation via blocking the progression from G1- to S-phase of the cell cycle, which is accompanied by elevated levels of myostatin and p21(Waf1/Cip1), and decreases in cyclin E and cyclin D1 expression. Our results suggest that syndecan-4 functions as a reservoir for promyostatin regulating the local bioavailability of mature myostatin.