Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway.
Sema4C is a member of transmembrane semaphorin proteins which regulate axonal guidance in the developing nervous system. The expression of Sema4C was dramatically induced not only during differentiation of C2C12 mouse myoblasts, but also during injury-induced skeletal muscle regeneration. C2C12 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 p38alpha-specific inhibitor SB203580. Knockdown of Sema4C by siRNA transfection during C2C12 myoblasts differentiation could suppress the phosphorylation of p38 followed by dramatically diminished myotube formation. Sema4C 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.
Wu
Haitao
H
Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
Wang
Xuan
X
Liu
Shuhong
S
Wu
Yan
Y
Zhao
Tong
T
Chen
Xiaoping
X
Zhu
Lingling
L
Wu
Yanrui
Y
Ding
Xuefeng
X
Peng
Xiaozhong
X
Yuan
Jiangang
J
Wang
Xiaomin
X
Fan
Wenhong
W
Fan
Ming
M
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004179:Cobra Cardiotoxin Proteins / Q000009:adverse effects / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000502:physiology*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D012038:Regeneration / Q000502:physiology; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004179:Cobra Cardiotoxin Proteins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018008:Myogenin; D011725:Pyridines; D034741:RNA, Small Interfering; C119353:Sema4c protein, mouse; D039961:Semaphorins; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580