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Regulation of IGFBP-2 expression during fasting
Kang, Hye ,Suk,Kim, Mi-Young,Kim, Seung-Jae,Lee, Jae-Ho,Kim, Yong-Deuk,Seo, Young-Kyo,Bae, Jae-Hoon,Oh, Goo-Taeg,Song, Dae-Kyu,Ahn, Yong-Ho,Im, Seung-Soon Portland Press Ltd. 2015 Biochemical journal Vol.467 No.3
<▼1><P>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 <I>Igfbp-2</I> gene by peroxisome-proliferator-activated receptor (PPAR) α in the liver. During fasting, both <I>Igfbp-2</I> and <I>PPARα</I> expression levels were increased. Wy14643, a selective PPARα agonist, significantly induced <I>Igfbp-2</I> gene expression in primary cultured hepatocytes. However, <I>Igfbp-2</I> gene expression in <I>Pparα</I> null mice was not affected by fasting or Wy14643. 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 <I>Igfbp-2</I> gene promoter, indicating that the <I>Igfbp-2</I> 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 <I>Pparα</I> null mice. These results suggest that PPARα controls IGF-1 signalling through the up-regulation of hepatic <I>Igfbp-2</I> transcription during fasting and Wy14643 treatment.</P></▼1><▼2><P>Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) is known to attenuate the biological action of IGF-1, but its regulatory mechanism remains unclear. We demonstrate the transcriptional regulation of the hepatic <I>Igfbp-2</I> gene by peroxisome-proliferator-activated receptor (PPAR) α during fasting. We also show how PPARα controls IGF-1 signalling through IGFBP-2.</P></▼2>