論文

査読有り
2009年4月

Transcription factor activating protein-2β: A positive regulator of monocyte chemoattractant protein-1 gene expression

Endocrinology
  • Motoyuki Kondo
  • ,
  • Hiroshi Maegawa
  • ,
  • Toshiyuki Obata
  • ,
  • Satoshi Ugi
  • ,
  • Kazuhiro Ikeda
  • ,
  • Katsutaro Morino
  • ,
  • Yukie Nakai
  • ,
  • Yoshihiko Nishio
  • ,
  • Shiro Maeda
  • ,
  • Atsunori Kashiwagi

150
4
開始ページ
1654
終了ページ
1661
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1210/en.2008-1361
出版者・発行元
4

We previously reported an association between the activating protein (AP)-2β transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2β showed stronger AP-2β expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2β leads to lipid accumulation by enhancing glucose transport and inducing insulin resistance in 3T3-L1 adipocytes. In this study, we found that overexpression of AP-2β in 3T3-L1 adipocytes accelerated the promoter activity of monocyte chemoattractant protein-1 (MCP-1) and subsequently increased both mRNA and protein expression and protein secretion. Furthermore, knockdown of endogenous AP-2β by RNA interference reduced the mRNA and the protein expression of MCP-1. EMSAs and chromatin immuno- precipitation assays revealed specific binding of AP-2β to MCP-1 promoter regions, in vitro and in vivo. Additionally, site-directed mutagenesis of the AP-2 binding site located at -137 to -129 relative to the transcription start site markedly diminished MCP-1 promoter activity, whereas other putative AP-2 binding sites did not. Our results clearly show that AP-2β directly enhanced MCP-1 secretion by binding to its promoter. Thus, we propose that AP-2β positively regulates MCP-1 expression
subsequently contributes to the infiltration of macrophages to adipose tissue
and leads to insulin resistance, type 2 diabetes, and cardiovascular diseases. Copyright © 2009 by The Endocrine Society.

リンク情報
DOI
https://doi.org/10.1210/en.2008-1361
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19022887

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