PMID- 19022887
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20090324
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 4
DP  - 2009 Apr
TI  - Transcription factor activating protein-2beta: a positive regulator of monocyte 
      chemoattractant protein-1 gene expression.
PG  - 1654-61
LID - 10.1210/en.2008-1361 [doi]
AB  - We previously reported an association between the activating protein (AP)-2beta 
      transcription factor gene and type 2 diabetes. This gene is preferentially 
      expressed in adipose tissue, and subjects with a disease-susceptible allele of 
      AP-2beta showed stronger AP-2beta expression in adipose tissue than those without 
      the susceptible allele. Furthermore, overexpression of AP-2beta 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-2beta 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-2beta by RNA 
      interference reduced the mRNA and the protein expression of MCP-1. EMSAs and 
      chromatin immunoprecipitation assays revealed specific binding of AP-2beta 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-2beta 
      directly enhanced MCP-1 secretion by binding to its promoter. Thus, we propose 
      that AP-2beta 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.
FAU - Kondo, Motoyuki
AU  - Kondo M
AD  - Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
FAU - Maegawa, Hiroshi
AU  - Maegawa H
FAU - Obata, Toshiyuki
AU  - Obata T
FAU - Ugi, Satoshi
AU  - Ugi S
FAU - Ikeda, Kazuhiro
AU  - Ikeda K
FAU - Morino, Katsutaro
AU  - Morino K
FAU - Nakai, Yukie
AU  - Nakai Y
FAU - Nishio, Yoshihiko
AU  - Nishio Y
FAU - Maeda, Shiro
AU  - Maeda S
FAU - Kashiwagi, Atsunori
AU  - Kashiwagi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081120
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factor AP-2)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Blotting, Western
MH  - Chemokine CCL2/*genetics/*metabolism
MH  - Chromatin Immunoprecipitation
MH  - DNA/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Mice
MH  - Plasmids/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA, Small Interfering
MH  - Response Elements/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factor AP-2/genetics/metabolism/*physiology
EDAT- 2008/11/22 09:00
MHDA- 2009/04/15 09:00
CRDT- 2008/11/22 09:00
PHST- 2008/11/22 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
PHST- 2008/11/22 09:00 [entrez]
AID - en.2008-1361 [pii]
AID - 10.1210/en.2008-1361 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Apr;150(4):1654-61. doi: 10.1210/en.2008-1361. Epub 2008 Nov 
      20.