| Literature DB >> 17950246 |
Atsutaka Yasui1, Hitoshi Nishizawa, Yosuke Okuno, Kentaro Morita, Hironori Kobayashi, Kenichiro Kawai, Morihiro Matsuda, Ken Kishida, Shinji Kihara, Yasutomi Kamei, Yoshihiro Ogawa, Tohru Funahashi, Iichiro Shimomura.
Abstract
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.Entities:
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Year: 2007 PMID： 17950246 DOI： 10.1016/j.bbrc.2007.10.013
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575