Regulation of IGFBP-2 expression during fasting

Hye Suk KangMi-Young KimSeung-Jae KimJae-Ho LeeYong-Deuk KimYoung-Kyo SeoJae-Hoon BaeGoo-Taeg OhDae-Kyu SongYong-Ho AhnSeung-Soon Im
Dept. of Anatomy (해부학); Dept. of Physiology (생리학)
Issue Date
Biochemical Journal, Vol.467(3) : 453-460, 2015
Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2), one of the most abundant circulating IGFBPs, is known to attenuate the biological action of IGF-1. Although the effect of IGFBP-2 in preventing metabolic disorders is well known, its regulatory mechanism remains unclear. In the present study, we demonstrated the transcriptional regulation of the Igfbp-2 gene by peroxisome-proliferator-activated receptor (PPAR) α in the liver. During fasting, both Igfbp-2 and PPARα expression levels were increased. Wy14643, a selective PPARα agonist, significantly induced Igfbp-2 gene expression in primary cultured hepatocytes. However, Igfbp-2 gene expression in Pparα micewas not affected by fasting orWy14643. In addition, through transient transfection and chromatin immunoprecipitation assay in fasted livers, we determined that PPARα bound to the putative PPAR-responsive element between −511 bp and −499 bp on the Igfbp-2 gene promoter, indicating that the Igfbp-2 gene transcription is activated directly by PPARα. To explore the role of PPARα in IGF-1 signalling, we treated primary cultured hepatocytes with Wy14643 and observed a decrease in the number of IGF-1 receptors (IGF-1Rs) and in Akt phosphorylation. No inhibition was observed in the hepatocytes isolated from Pparα mice. These results suggest that PPARα controls IGF-1 signalling through the up-regulation of hepatic Igfbp-2 transcription during fasting and Wy14643 treatment. Key words: fasting, gene expression, insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2), liver, peroxisome-proliferator-activated receptor α (PPARα).
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Anatomy (해부학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
Keimyung Author(s)
이재호; 배재훈; 송대규; 임승순
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