Resistin is expressed in human macrophages and directly regulated by PPARγ activators

被引:777
作者
Patel, L [1 ]
Buckels, AC
Kinghorn, IJ
Murdock, PR
Holbrook, JD
Plumpton, C
Macphee, CH
Smith, SA
机构
[1] GlaxoSmithKline, Dept Atherosclerosis, Stevenage SG1 2NY, Herts, England
[2] GlaxoSmithKline, Dept Gene Express & Prot Biochem, Stevenage SG1 2NY, Herts, England
[3] GlaxoSmithKline, Dept Gene Express, Harlow CM19 5AD, Essex, England
[4] GlaxoSmithKline, Dept Bioinformat, Harlow CM19 5AD, Essex, England
[5] GlaxoSmithKline, Dept Vasc Biol, Philadelphia, PA USA
[6] GlaxoSmithKline, Dept Global Commercial Strategy, Harlow CM19 5AD, Essex, England
关键词
PPAR gamma; rosiglitazone; monocyte; macrophage; resistin;
D O I
10.1016/S0006-291X(02)02841-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Resistin is a cysteine-rich protein postulated to be a molecular link between obesity and type 2 diabetes. The aim of this study was to investigate the role of PPARgamma in the regulation of resistin expression in human primary macrophages. Fluorescent real-time PCR (Taqman) analysis of resistin expression across a range of human tissues showed that resistin is highly expressed in bone marrow compared to other tissues. Taqman analysis and Western blotting showed that rosiglitazone decreased resistin expression at both the mRNA and protein levels in human primary monocyte-derived macrophages in vitro. Resistin expression was reduced by up to 80% after exposure to 100nM rosiglitazone for 96 h. Bioinformatics analysis of the genomic sequence upstream of the resistin coding sequence identified several putative PPAR response elements of which one was shown to bind PPARgamma using electrophoretic mobility shift assays. Our data support a direct role for PPARgamma in the regulation of resistin expression. (C) 2002 Flsevier Science (USA). All rights reserved.
引用
收藏
页码:472 / 476
页数:5
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