Possible role of TIEG1 as a feedback regulator of myostatin and TGF-beta in myoblasts.
Myostatin and TGF-beta negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-beta signaling remains unclear. TGF-beta inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-beta signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-beta signaling using C2C12 myoblasts. Myostatin and TGF-beta induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-beta enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-beta in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-beta. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-beta that prevents excess action in myoblasts.
Miyake
Masato
M
Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555, Japan.
Hayashi
Shinichiro
S
Iwasaki
Shunsuke
S
Chao
Guozheng
G
Takahashi
Hideyuki
H
Watanabe
Kouichi
K
Ohwada
Shyuichi
S
Aso
Hisashi
H
Yamaguchi
Takahiro
T
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
D004268:DNA-Binding Proteins; D055435:Myostatin; D051785:Smad Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors