Possible role of TIEG1 as a feedback regulator of myostatin and TGF-β in myoblasts

Masato Miyake, Shinichiro Hayashi, Shunsuke Iwasaki, Guozheng Chao, Hideyuki Takahashi, Kouichi Watanabe, Shyuichi Ohwada, Hisashi Aso, Takahiro Yamaguchi

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Myostatin and TGF-β negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-β signaling remains unclear. TGF-β inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-β signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-β signaling using C2C12 myoblasts. Myostatin and TGF-β 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-β enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-β 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-β. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-β that prevents excess action in myoblasts.

    Original languageEnglish
    Pages (from-to)762-766
    Number of pages5
    JournalBiochemical and biophysical research communications
    Volume393
    Issue number4
    DOIs
    Publication statusPublished - 2010 Mar 19

    Keywords

    • Myoblast
    • Myostatin
    • Skeletal muscle
    • Smad
    • TGF-β
    • TIEG1

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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