Inhibition of myogenesis by transforming growth factor β is density- dependent and related to the translocation of transcription factor MEF2 to the cytoplasm

L. De Angelis, S. Borghi, R. Melchionna, L. Berghella, M. Baccarani-Contri, F. Parise, S. Ferrari, G. Cossu

Research output: Contribution to journalArticle

Abstract

Transforming growth factor β (TGF-β) was found to inhibit differentiation of myogenic cells only when they were grown to high density. Inhibition also occurred when myogenic cells were cocultured with other types of mesenchymal cells but not when they were cocultured with epithelial cells. It is therefore possible that some density-dependent signaling mediates the intracellular response to TGF-β. Within 30 min of treatment, TGF-β induced translocation of MEF2, but not MyoD, myogenin, or p21, to the cytoplasm of myogenic cells grown to high density. Translocation was reversible on withdrawal of TGF-β. By using immune electron microscopy and Western blot analysis on subcellular fractions, MEF2 was shown to be tightly associated with cytoskeleton membrane components. To test whether MEF2 export from the nucleus was causally related to the inhibitory action of TGF-β, we transfected C2C12 myoblasts with MEF2C containing the nuclear localization signal of simian virus 40 large T antigen (nlsSV40). Myogenic cells expressing the chimerical MEF2C/nlsSV40, but not wild-type MEF2C, retained this transcription factor in the nucleus and were resistant to the inhibitory action of TGF-β. We propose a mechanism in which the inhibition of myogenesis by TGF-β is mediated through MEF2 localization to the cytoplasm, thus preventing it from participating in an active transcriptional complex.

Original languageEnglish
Pages (from-to)12358-12363
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number21
DOIs
Publication statusPublished - Oct 13 1998

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MEF2 Transcription Factors
Muscle Development
Transforming Growth Factors
Cytoplasm
Nuclear Localization Signals
Simian virus 40
Viral Tumor Antigens
Myogenin
Subcellular Fractions
Myoblasts
Cytoskeleton
Cell Differentiation
Electron Microscopy
Western Blotting
Epithelial Cells
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

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Inhibition of myogenesis by transforming growth factor β is density- dependent and related to the translocation of transcription factor MEF2 to the cytoplasm. / De Angelis, L.; Borghi, S.; Melchionna, R.; Berghella, L.; Baccarani-Contri, M.; Parise, F.; Ferrari, S.; Cossu, G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 21, 13.10.1998, p. 12358-12363.

Research output: Contribution to journalArticle

De Angelis, L. ; Borghi, S. ; Melchionna, R. ; Berghella, L. ; Baccarani-Contri, M. ; Parise, F. ; Ferrari, S. ; Cossu, G. / Inhibition of myogenesis by transforming growth factor β is density- dependent and related to the translocation of transcription factor MEF2 to the cytoplasm. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 21. pp. 12358-12363.
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