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Regulation of IGFBP-2 expression during fasting

Title
Regulation of IGFBP-2 expression during fasting
Authors
Kang H.S.Kim M.-Y.Kim S.-J.Lee J.-H.Kim Y.-D.Seo Y.-K.Bae J.-H.Oh G.-T.Song D.-K.Ahn Y.-H.Im S.-S.
Ewha Authors
오구택
SCOPUS Author ID
오구택scopus
Issue Date
2015
Journal Title
Biochemical Journal
ISSN
0264-6021JCR Link
Citation
vol. 467, no. 3, pp. 453 - 460
Keywords
FastingGene expressionInsulin-like growth factor-1 (IGF-1)Insulin-like growth factor-binding protein 2 (IGFBP-2)LiverPeroxisome-proliferator-activated receptor α (PPARα)
Publisher
Portland Press Ltd
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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 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 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. © The Authors Journal compilation © 2015 Biochemical Society.
DOI
10.1042/BJ20141248
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자연과학대학 > 생명과학전공 > Journal papers
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