Article

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

Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 01/2008; 364(2):358-65. DOI: 10.1016/j.bbrc.2007.10.013
Source: PubMed

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.

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    • "1B), or PCR for mRNA (1±.09, .89±.17, 2.63±.55 AU, n=6, 3, and 6 for TG, GFP and WT respectively, p<.05 for TG vs. GFP or WT Regulation of musclin transcription has been linked to FOXO1 activity [21,23,27]. As demonstrated in cell culture and in vivo, nuclear export of FOXO1 releases transcription of the musclin gene from inhibition [23,26]. "
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    DESCRIPTION: Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin
    Full-text · Research · Feb 2016
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    • "1B), or PCR for mRNA (1±.09, .89±.17, 2.63±.55 AU, n=6, 3, and 6 for TG, GFP and WT respectively, p<.05 for TG vs. GFP or WT Regulation of musclin transcription has been linked to FOXO1 activity [21,23,27]. As demonstrated in cell culture and in vivo, nuclear export of FOXO1 releases transcription of the musclin gene from inhibition [23,26]. "

    Full-text · Article · Jan 2016 · Biochemical and Biophysical Research Communications
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    • "In addition, we used the ab14355 anti-NPR-C antibody to abolish the vasoconstriction caused by musclin in order to highlight the mediation of NPR-C. The first (88LDRL91) and second (117MDRI120) NP-homologous regions of musclin are responsible for the cooperative high-affinity binding to NPR-C [3]. The binding of musclin with NPR-C has been demonstrated by assessing the competition with ANP [3]. "
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    ABSTRACT: Musclin is a novel skeletal muscle-derived secretory factor found in the signal sequence trap of mouse skeletal muscle cDNAs. Musclin possesses a region homologous to the natriuretic peptide family. Thus, musclin is found to bind with the natriuretic peptide clearance receptors. However, the role of musclin in vascular regulation remains unclear. In this study, we aim to investigate the direct effect of musclin on vascular tone and to analyze its role in hypertension using the spontaneously hypertensive rats (SHR). In aortic strips isolated from SHR, musclin induced contractions in a dose-dependent manner. We found that the musclin-induced vasoconstriction was more marked in SHR than in normal rats (WKY). Moreover, this contraction was reduced by blockade of natriuretic peptide receptor C using the ab14355 antibody. Therefore, mediation of the natriuretic peptide receptor in musclin-induced vasoconstriction can be considered. In addition, similar to the natriuretic peptide receptor, expression of the musclin gene in blood vessels was higher in SHR than in WKY. Injection of musclin markedly increased the blood pressure in rats that can be inhibited by anti-musclin antibodies. Musclin-induced vasoconstriction was more pronounced in SHR than in WKY as in its expression. Taken together, these results suggest that musclin is involved in blood pressure regulation. The higher expression of musclin in hypertension indicates that musclin could be used as a new target for the treatment of hypertension in the future.
    Preview · Article · Aug 2013 · PLoS ONE
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