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Regulation of IGFBP-2 expression during fasting

 Hye Suk Kang  ;  Mi-Young Kim  ;  Seung-Jae Kim  ;  Jae-Ho Lee  ;  Yong-Deuk Kim  ;  Young-Kyo Seo  ;  Jae-Hoon Bae  ;  Goo-Taeg Oh  ;  Dae-Kyu Song  ;  Yong-Ho Ahn  ;  Seung-Soon Im 
 BIOCHEMICAL JOURNAL, Vol.467(3) : 453-460, 2015 
Journal Title
Issue Date
Animals ; Cells, Cultured ; Fasting/metabolism* ; Gene Expression Regulation/drug effects ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Insulin-Like Growth Factor Binding Protein 2/genetics* ; Insulin-Like Growth Factor I/metabolism ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; PPAR alpha/deficiency ; PPAR alpha/genetics ; PPAR gamma/agonists ; Peroxisome Proliferators/pharmacology ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Pyrimidines/pharmacology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Signal Transduction ; Thiazolidinediones/pharmacology ; Up-Regulation/drug effects
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)
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 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 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 null mice. These results suggest that PPARα controls IGF-1 signalling through the up-regulation of hepatic Igfbp-2 transcription during fasting and Wy14643 treatment.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
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