| PPARδ increases expression of the human apolipoprotein A-II gene in human liver cells |
Authors: Petra Thulin, Björn Glinghammar, Josefin Skogsberg, Kerstin Lundell, Ewa Ehrenborg |
Affiliations:
Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. petra.thulin@ki.se
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Pages: 819-824 |
Abstract:
The peroxisome proliferator-activated receptor δ (PPARδ) is a transcription factor that regulates genes of importance in lipid and glucose metabolism. ApoA-II is one of the major proteins of the HDL-particle. The aim of this study was to investigate the regulation of apoA-II gene expression by PPARδ. Treatment of HepG2 cells with the PPARδ specific agonist GW501516 increased apoA-II mRNA expression. Likewise, reporter gene assays using a construct containing 2.7 kb of the proximal apoA-II promoter showed increased activity after treatment with GW501516, both in HepG2 and in HuH-7 cells. Mutation of two putative PPAR response elements (PPREs) in this region showed that the PPRE at position -737/-717 is the functional site. Binding of PPARδ to this site was confirmed by chromatin immunoprecipitation and gel retardation analyses. In conclusion, PPARδ increases the expression of the human apoA-II gene in liver cells via a PPRE in the proximal promoter.
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