Foxo1 represses expression of musclin, a skeletal muscle-derived secretory factor

Atsutaka Yasui, Hitoshi Nishizawa, Yosuke Okuno, Kentaro Morita, Hironori Kobayashi, Kenichiro Kawai, Morihiro Matsuda, Ken Kishida, Shinji Kihara, Yasutomi Kamei, Yoshihiro Ogawa, Tohru Funahashi, Iichiro Shimomura

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28 Citations (Scopus)


Musclin is a novel skeletal muscle-derived secretory factor, whose mRNA level is markedly regulated by nutritional status. In the present study, we investigated the mechanism of musclin mRNA regulation by insulin. In C2C12 myocytes, insulin-induced upregulation of musclin mRNA was significantly decreased by treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and was abolished in C2C12 myocytes stably expressing a constitutively active Foxo1 (Foxo1-3A), suggesting the involvement of Foxo1 in the regulation of musclin mRNA. Promoter deletion analysis of musclin promoter revealed that the region of -303/-123 is important for the repression of promoter activity by Foxo1. Chromatin immunoprecipitation assay showed that Foxo1 bound to musclin promoter. Musclin mRNA level was markedly downregulated in gastrocnemius muscle of Foxo1 transgenic mice. Our results demonstrated that Foxo1 downregulates musclin mRNA expression both in vitro and in vivo, which should explain insulin-mediated upregulation of this gene in muscle cells.

Original languageEnglish
Pages (from-to)358-365
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Dec 14 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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