Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway
Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway
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Sema4C 通过 p38 MAPK 途径参与体内和体外的肌原性分化。
DOI：
10.1016/j.ejcb.2007.03.002
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发表时间：
2007-06-01
影响因子：
6.6
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Wu, Haitao;Wang, Xuan;Fan, Ming
Serna4C是跨膜sernaphorin蛋白的成员，其调节发育神经系统中的轴突引导。Sema4C的表达不仅在C2Cl2小鼠成肌细胞分化过程中被显著诱导，而且在损伤诱导的骨骼肌再生过程中也被显著诱导。稳定或瞬时表达Sema4C的C2Cl2细胞均表现出由加速的肌管形成和肌肉特异性蛋白表达反映的肌源性分化增加。过表达Sema4C可直接诱导p38磷酸化，p38 α特异性抑制剂SB 203580可阻断Sema4C在成肌分化中的作用。在C2Cl2成肌细胞分化过程中通过siRNA转染敲低Sema4C可以抑制p38的磷酸化，随后显著减少肌管形成。Serna4C在成肌分化过程中可激活myogenin启动子。p38抑制剂SB203580可阻断这种激活作用。两者合计，这些观察结果揭示了新的功能潜力的Sema4C，这表明Sema4C促进终末成肌分化的p38 MAPK依赖的方式。(c)2007年爱思唯尔有限公司。All rights reserved.
Serna4C is a member of transmembrane sernaphorin proteins which regulate axonal guidance in the developing nervous system. The expression of Sema4C was dramatically induced not only during differentiation of C2Cl2 mouse myoblasts, but also during injury-induced skeletal muscle regeneration. C2Cl2 cells stably or transiently expressing Sema4C both showed increased myogenic differentiation reflected by accelerated myotube formation and expression of muscle-specific proteins. Overexpression of Sema4C elicited p38 phosphorylation directly, and the effects of Sema4C during myogenic differentiation could be abolished by the p38 alpha-specific inhibitor SB203580. Knockdown of Sema4C by siRNA transfection during C2Cl2 myoblasts differentiation could suppress the phosphorylation of p38 followed by dramatically diminished myotube formation. Serna4C could activate the myogenin promoter during myogenic differentiation. This activation could be abolished by p38 inhibitor SB203580. Taken together, these observations reveal novel functional potentialities of Sema4C which suggest that Sema4C promotes terminal myogenic differentiation in a p38 MAPK-dependent manner. (c) 2007 Elsevier GmbH. All rights reserved.