title: CYP19A1, MIF and ABCA1 genes are targets of the RORα in monocyte and endothelial cells.
abstract: RORα is a member of nuclear receptor superfamily of transcription factors, which has a vital role in the regulation of various physiological processes. Cholesterol is a known ligand of RORα and is one of the key components that take part in cardiovascular diseases such as atherosclerosis. Therefore, it is possible that RORα might have a role in the development of atherosclerosis. To test this hypothesis, we investigated the presence of novel RORα response elements (ROREs) located in the promoter of CYP19A1, MIF and ABCA1 genes. Briefly, the occupancy of RORα in the promoter regions of these genes was demonstrated in THP-1 and HUVEC cell lines by ChIP analysis. In order to modulate RORα activity, THP-1 and HUVEC cells were treated with specific RORα ligands (CPG 52608 and SR1001) and then the expression levels of target genes were analysed. In the next step, we tested whether RORα activity in THP-1 macrophages was influenced by the presence of simvastatin, a cholesterol lowering drug. We found that in the presence of simvastatin the expression of the investigated target genes were down regulated and that this regulation was partially prevented by CPG 52608 and SR1001. Results of this study suggest that CYP19A1, MIF and ABCA1 are the direct target genes of RORα. In conclusion, it is important to demonstrate that certain genes involved in the development of atherosclerosis could be modulated by an inducible transcription factor. Therefore, these results offer a potential therapeutic approach for the treatment of atherosclerosis.
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Vakif Gureba Cad. 34080 Sehremini, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Coban
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Vakif Gureba Cad. 34080 Sehremini, Istanbul, Turkey.
authors.forename: Cagri
authors.initials: C
authors.lastname: Gulec
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Vakif Gureba Cad. 34080 Sehremini, Istanbul, Turkey.
authors.forename: Bilge
authors.initials: B
authors.lastname: Ozsait-Selcuk
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Vakif Gureba Cad. 34080 Sehremini, Istanbul, Turkey.
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Unaltuna
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000378:metabolism; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008024:Ligands; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008024:Ligands; D008263:Macrophage Migration-Inhibitory Factors; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; C558809:SR1001; D013449:Sulfonamides; D013844:Thiazoles; D019821:Simvastatin; D001141:Aromatase; C561410:CYP19A1 protein, human; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: ABCA1; CYP19A1; ChIP; MIF; RORα; simvastatin